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Budi, Luh Putu Rihayani, Ketut Ariawati et Sianny Herawati. « NEONATAL ACUTE MYELOID LEUKAEMIA ». INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 19, no 3 (14 octobre 2016) : 211. http://dx.doi.org/10.24293/ijcpml.v19i3.417.
Texte intégralRésumé :
Acute myeloid leukaemia (AML) is a. malignant, clonally disease that involves proliferation of blasts in bone marrow, blood, or other tissue. The blasts most often show myeloid or monocytic differentiation. The incidence of AML increases with age, but when neonatal leukaemia does occur, it is paradoxically AML rather than ALL. All the signs and symptoms that present on patient with AML are caused by the infiltration of the bone marrow with leukaemic cells and resulting failure of normal haematopoiesis. Without the normal haematopoietic elements, the patient is at risk for developing life-threatening complications of anaemia, infection due to functional neutropenia, and haemorrhage due to thrombocytopenia. Organomegaly is seen in approximately half of patient with AML due to hepatic and sphlanic infiltration with leukaemic blasts. Prognosis of neonatal leukaemia is poor with the 6-month survival rate is only one third despite aggressive chemotherapy. It has higher mortality rate than any other congenital cancer. The researchers reported two of AML diagnosed cases in neonatal period. The first case, a one-day-old male was referred with respiratory distress and suspect Down syndrome with spontaneous petechiae. The second case, a 17-day-old female presented with bloody diarrhoea and history of hypothyroid. Dysmorphic face and hepatosplenomegalia were found in both of the physical examination. Their complete blood count revealed leukocytosis and thrombocytopenia. Peripheral blood smear revealed myeloblast 30% on the first case and 23% on the second case. Both immunophenotyping revealed the population of blast expressing myeloid lineage (CD33 and CD34).
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Nurunnabi, Md, Mosammath Khadiza Mamdu, Ayesha Siddika, Farzana Zafreen, Md Abdul Wahab et Shahana Shermin. « Morphological and Immunophenotypic Analysis in Diagnosis of Acute Leukaemia ». Delta Medical College Journal 8, no 1 (31 mars 2022) : 15–20. http://dx.doi.org/10.3329/dmcj.v8i1.58958.
Texte intégralRésumé :
Background: Leukaemias are neoplastic proliferations of haematopoietic stem cells and form a major proportion of haematopoietic neoplasms that are diagnosed worldwide.
Objective: To differentiate between morphological and immunophenotypic analysis in the diagnosis of acute leukemia.
Materials and method: This cross sectional study was conducted in the department of Haematology, Armed Forces Institute of Pathology (AFIP), Dhaka, Bangladesh from January 2008 to December 2008. Total 50 patients were included after fulfilling inclusion and exclusion criteria.
Results: The total of 50 bone marrow samples from suspected cases of acute leukaemia were included in the study. Out of 50 samples, 48 cases were diagnosed as either acute myeloid leukaemia (19 or 38%) or acute lymphoblastic leukaemia (29 or 58%) and 02 (04%) cases were morphologically indistinguishable. All 50 cases were subjected to immunophenotypic study. Out of 50 cases immunophenotypically 14(28%) were acute myeloid leukaemia (AML), 32(64%) were acute lymphoblastic leukaemia (ALL), and bi-phenotypic leukaemia and acute undifferentiated leukaemia were 02(04%) each. In this study Male: Female ratio was 1.3:1. Out of 19(38%) cases of AML, 29(58%) cases of ALL and 02(04%) cases of indistinguishable diagnosed morphologically, 14(28%) were found to be AML, 32(64%) ALL, 02(04%) bi-phenotypic and 02(04%) were acute undifferentiated leukaemias on immunophenotyping respectively. Out of 29 cases identified as ALL on morphology 25(86.2%) were confirmed as ALL, 02(07%) turned out to be AML, 01(3.4%) was bi-phenotypic and 01(3.4%) was undifferentiated.
Conclusion: In this study, acute lymphoblastic leukaemia was the commonest type of leukemia followed by acute myeloid leukaemia with male predominance seen in all types of leukaemia.
Delta Med Col J. Jul 2020 8(1): 15-20
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Gruszka, Alicja, Debora Valli, Cecilia Restelli et Myriam Alcalay. « Adhesion Deregulation in Acute Myeloid Leukaemia ». Cells 8, no 1 (17 janvier 2019) : 66. http://dx.doi.org/10.3390/cells8010066.
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Cell adhesion is a process through which cells interact with and attach to neighboring cells or matrix using specialized surface cell adhesion molecules (AMs). Adhesion plays an important role in normal haematopoiesis and in acute myeloid leukaemia (AML). AML blasts express many of the AMs identified on normal haematopoietic precursors. Differential expression of AMs between normal haematopoietic cells and leukaemic blasts has been documented to a variable extent, likely reflecting the heterogeneity of the disease. AMs govern a variety of processes within the bone marrow (BM), such as migration, homing, and quiescence. AML blasts home to the BM, as the AM-mediated interaction with the niche protects them from chemotherapeutic agents. On the contrary, they detach from the niches and move from the BM into the peripheral blood to colonize other sites, i.e., the spleen and liver, possibly in a process that is reminiscent of epithelial-to-mesenchymal-transition in metastatic solid cancers. The expression of AMs has a prognostic impact and there are ongoing efforts to therapeutically target adhesion in the fight against leukaemia.
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Gruszka, Alicja M., Debora Valli et Myriam Alcalay. « Wnt Signalling in Acute Myeloid Leukaemia ». Cells 8, no 11 (7 novembre 2019) : 1403. http://dx.doi.org/10.3390/cells8111403.
Texte intégralRésumé :
Acute myeloid leukaemia (AML) is a group of malignant diseases of the haematopoietic system. AML occurs as the result of mutations in haematopoietic stem/progenitor cells, which upregulate Wnt signalling through a variety of mechanisms. Other mechanisms of Wnt activation in AML have been described such as Wnt antagonist inactivation through promoter methylation. Wnt signalling is necessary for the maintenance of leukaemic stem cells. Several molecules involved in or modulating Wnt signalling have a prognostic value in AML. These include: β-catenin, LEF-1, phosphorylated-GSK3β, PSMD2, PPARD, XPNPEP, sFRP2, RUNX1, AXIN2, PCDH17, CXXC5, LLGL1 and PTK7. Targeting Wnt signalling for tumour eradication is an approach that is being explored in haematological and solid tumours. A number of preclinical studies confirms its feasibility, albeit, so far no reliable clinical trial data are available to prove its utility and efficacy.
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Niazmand, Mohammad Javad, Matthew Speckert et Donna Johnston. « Acute myeloid leukaemia presenting as proptosis in an infant ». BMJ Case Reports 14, no 12 (décembre 2021) : e247506. http://dx.doi.org/10.1136/bcr-2021-247506.
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Paediatric patients with acute myeloid leukaemia (AML) often present with symptoms associated with the disruption of normal haematopoiesis and subsequent cellular deficiencies. Periosteal reactions are common in paediatric leukaemia, but typically manifest as a thin, laminated pattern along long bones. Aggressive periosteal reactions are much less frequently seen. Here, we report a case of paediatric AML initially presenting with proptosis and periorbital swelling caused by aggressive, sunburst periosteal reactions surrounding the sphenoid and zygomatic bones. This unique presentation emphasises the importance of considering leukaemic infiltration in the differential for sunburst periosteal reaction in paediatric patients.
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Sun, Qian, Chi-Chiu So, Sze-Fai Yip, Thomas S. K. Wan, Edmond Shiu Kwan Ma et LiChong Chan. « Functional Alterations of Lin−CD34+CD38+ Progenitors in Chronic Myelomonocytic Leukaemia and on Progression to Acute Leukaemia. » Blood 110, no 11 (16 novembre 2007) : 4119. http://dx.doi.org/10.1182/blood.v110.11.4119.4119.
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Abstract Chronic myelomonocytic leukaemia (CMML) is a clonal bone marrow stem cell disorder based on the presence of trilineage involvement, the association of myelodysplastic and myeloproliferative features and its ability to transform into acute myeloid leukaemia. The objectives of our study are to identify the cell population and its functional characteristics involved in evolution from CMML phase to acute myeloid leukaemia. We analysed Lin−CD34+ stem/progenitor population and performed cell proliferation, apoptotic assays, self-renewal ability and differentiation potential studies in purified populations of Lin−CD34+CD38− stem cells and Lin−CD34+CD38+ committed progenitors from peripheral blood of 16 patients with CMML and in six of the 16 after transformation to acute myeloid leukaemia (AML-t). We observed an expansion of the stem cell/progenitor pool (Lin−CD34+ cells) in AML-t comprising mainly of Lin−CD34+CD38+ committed progenitors within Lin−CD34+ cells. The Lin−CD34+CD38+ committed progenitors displayed highly proliferative activity in CMML and in AML-t; and additionally acquired resistance to apotosis and myeloid colony self-renewing ability in AML-t. Impairment of dendritic cell (DC) differentiation was observed with complete block in AML-t. Our findings suggest Lin−CD34+CD38+ committed progenitors instead of Lin−CD34+CD38− stem cells could be the target(s) of secondary genetic lesions underpinning progression from CMML to AML. These results have implications for the further study of the biology of leukaemic transformation and the design of new strategies for the effective treatment of CMML.
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Skarsgård, Lisa Stenman, Mattias K. Andersson, Marta Persson, Ann-Cathrine Larsen, Sarah E. Coupland, Göran Stenman et Steffen Heegaard. « Clinical and genomic features of adult and paediatric acute leukaemias with ophthalmic manifestations ». BMJ Open Ophthalmology 4, no 1 (octobre 2019) : e000362. http://dx.doi.org/10.1136/bmjophth-2019-000362.
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ObjectiveTo describe the clinicopathological and genomic features of nine patients with primary and secondary orbital/ocular manifestations of leukaemia.MethodsAll orbital/ocular leukaemic specimens from 1980 to 2009 were collected from the Danish Register of Pathology. In six cases, medical records and formalin-fixed, paraffin-embedded blocks were available. Three cases from the Department of Pathology, Royal Liverpool University Hospital, were also included. Immunophenotypes and MYB oncoprotein expression were ascertained by immunohistochemistry. Genomic imbalances were analysed with comparative genomic hybridisation arrays and oncogene rearrangements with fluorescence in situ hybridisation.ResultsFour patients had B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) and five had acute myeloid leukaemia (AML). Two patients with BCP-ALL and one with AML had primary orbital manifestations of leukaemia. Common symptoms were proptosis, displacement of the eye, and reduced eye mobility in patients with orbital leukaemias and pain, and reduced visual acuity in patients with ocular leukaemias. All patients with primary orbital lesions were alive up to 18 years after diagnosis. All but one patient with secondary ophthalmic manifestations died of relapse/disseminated disease. ETV6 and RUNX1 were rearranged in BCP-ALL, and RUNX1 and KMT2A in AML. Genomic profiling revealed quiet genomes (0–7 aberrations/case). The MYB oncoprotein was overexpressed in the majority of cases.ConclusionsLeukaemias with and without ophthalmic manifestations have similar immunophenotypes, translocations/gene fusions and copy number alterations. Awareness of the clinical spectrum of leukaemic lesions of the eye or ocular region is important to quickly establish the correct diagnosis and commence prompt treatment.
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Arruda, Walter Oleschko, María Belén Montú, Marcelo de Souza R. de Oliveira et Ricardo Ramina. « Acute myeloid leukaemia induced by mitoxantrone : case report ». Arquivos de Neuro-Psiquiatria 63, no 2a (juin 2005) : 327–29. http://dx.doi.org/10.1590/s0004-282x2005000200024.
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Mitoxantrone (MX) is an immunosupressant drug used in secondarily progressive multiple sclerosis (SPMS) and in relapsing-remitting multiple sclerosis (RRMS). It has a leukemogenesis potential induced by cytogenetic abnormalities, though with a low incidence. Promyelocitic leukaemia (type M3) and other forms of acute myeloblastic leukaemias (M4 and M5) have been described in a few MS patients who received MX during their treatment. We describe a white female patient, 47 year-old, with SPMS (EDSS = 4) with 14 years of disease. She received MX during her disease and developed acute promyelocytic leukaemia (M3), with severe thrombocytopenia 30 months later. She ultimately died due to intracerebral hemorrhage. Other cases of treatment related to AML are reviewed and discussed.
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Sarrou, Evgenia, Laura Richmond, Ruaidhrí J. Carmody, Brenda Gibson et Karen Keeshan. « CRISPR Gene Editing of Murine Blood Stem and Progenitor Cells Induces MLL-AF9 Chromosomal Translocation and MLL-AF9 Leukaemogenesis ». International Journal of Molecular Sciences 21, no 12 (15 juin 2020) : 4266. http://dx.doi.org/10.3390/ijms21124266.
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Chromosomal rearrangements of the mixed lineage leukaemia (MLL, also known as KMT2A) gene on chromosome 11q23 are amongst the most common genetic abnormalities observed in human acute leukaemias. MLL rearrangements (MLLr) are the most common cytogenetic abnormalities in infant and childhood acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL) and do not normally acquire secondary mutations compared to other leukaemias. To model these leukaemias, we have used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing to induce MLL-AF9 (MA9) chromosomal rearrangements in murine hematopoietic stem and progenitor cell lines and primary cells. By utilizing a dual-single guide RNA (sgRNA) approach targeting the breakpoint cluster region of murine Mll and Af9 equivalent to that in human MA9 rearrangements, we show efficient de novo generation of MA9 fusion product at the DNA and RNA levels in the bulk population. The leukaemic features of MA9-induced disease were observed including increased clonogenicity, enrichment of c-Kit-positive leukaemic stem cells and increased MA9 target gene expression. This approach provided a rapid and reliable means of de novo generation of Mll-Af9 genetic rearrangements in murine haematopoietic stem and progenitor cells (HSPCs), using CRISPR/Cas9 technology to produce a cellular model of MA9 leukaemias which faithfully reproduces many features of the human disease in vitro.
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Palma, Catalina A., Elise Tonna, Adam J. Bryant, Vivek Jayaswal, David Agapiou, Yee Hwa Yang, David Ma et Mark Lutherborrow. « MicroRNA Expression in Acute Myeloid Leukaemia and Their Effects on the Differentiation of Acute Myeloid Leukaemia Cells ». Blood 118, no 21 (18 novembre 2011) : 2430. http://dx.doi.org/10.1182/blood.v118.21.2430.2430.
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Abstract Abstract 2430 Acute myeloid leukaemia (AML) is typified by an aberrant halt in maturation of myeloid progenitor cells, leading to uncontrolled proliferation of immature blasts. In the majority of cases of AML with normal karyotype, the underlying cause of the maturation arrest remains unclear. MicroRNAs, small inhibitory RNAs, are known to be dysregulated in cancers and have been postulated to play a causative role in leukaemogenesis. We aimed to investigate the contribution of aberrant microRNA expression to the inhibition of maturation in AML cells. MicroRNA expression profiling was performed on the bone marrow of 28 AML patients with normal karyotype and 8 normal controls. Differential expression was confirmed by qRT-PCR. We found that the expression of a panel of 12 microRNAs was able to accurately separate AML-M1 and AML-M5 subtypes. The AML-M1 subtype represents a more immature cell population when compared to the monoblast morphology observed in AML-M5. Four candidate microRNAs, miR-181a, -146a, -130a and -135b were selected for further investigation based in their putative targeting of key monocytic transcription factors as determined by in silico modelling followed by luciferase assays. In vitro monocyte and macrophage differentiation of HL60 and NB4 cell lines with 1,25-dihydroxyvitamin D3 and/or phorbol-12-myristate-13-acetate treatment resulted in a significant decrease in all four candidate microRNAs (measured by qRT-PCR), supporting the hypothesis that candidate microRNA over-expression in AML-M1 may contribute to its maturation arrest. Over-expression of the candidate microRNAs by transfection with Pre-miR microRNA precursor molecules (Ambion) into the HL60 and NB4 monocyte differentiation model, resulted in the significant suppression of CD14 (Figure, *p <0.05 compared to Scrambled control) and CD15 expression, markers of monocytes and granulocytes respectively. Conversely, knockdown of miR-181a, -146a, -130a and -135b with miRCURY LNA microRNA knockdown probes (Exiqon) induced an increase in CD14 expression in HL60 cells compared to non-targeting Scrambled control. An important regulatory role of these microRNAs in myeloid/monocytic differentiation is strongly suggested by their targeted suppression of the key transcription factors KLF4, MAFB, IRF8, HOXA10, MCL1 and PU.1 which was confirmed by luciferase reporter assay. This study provides evidence that the over-expressed microRNAs discovered in our profiling work between AML-M1 and AML-M5 are biologically relevant microRNAs, which have the potential to affect the maturation potential of AML cells. Disclosures: No relevant conflicts of interest to declare.
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Khan, Ghazala, Kim Orchard et Barbara-ann Guinn. « Antigenic Targets for the Immunotherapy of Acute Myeloid Leukaemia ». Journal of Clinical Medicine 8, no 2 (23 janvier 2019) : 134. http://dx.doi.org/10.3390/jcm8020134.
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One of the most promising approaches to preventing relapse is the stimulation of the body’s own immune system to kill residual cancer cells after conventional therapy has destroyed the bulk of the tumour. In acute myeloid leukaemia (AML), the high frequency with which patients achieve first remission, and the diffuse nature of the disease throughout the periphery, makes immunotherapy particularly appealing following induction and consolidation therapy, using chemotherapy, and where possible stem cell transplantation. Immunotherapy could be used to remove residual disease, including leukaemic stem cells from the farthest recesses of the body, reducing, if not eliminating, the prospect of relapse. The identification of novel antigens that exist at disease presentation and can act as targets for immunotherapy have also proved useful in helping us to gain a better understand of the biology that belies AML. It appears that there is an additional function of leukaemia associated antigens as biomarkers of disease state and survival. Here, we discuss these findings.
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Skelding, Kathryn A., Daniel L. Barry, Danielle Z. Theron et Lisa F. Lincz. « Bone Marrow Microenvironment as a Source of New Drug Targets for the Treatment of Acute Myeloid Leukaemia ». International Journal of Molecular Sciences 24, no 1 (29 décembre 2022) : 563. http://dx.doi.org/10.3390/ijms24010563.
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Acute myeloid leukaemia (AML) is a heterogeneous disease with one of the worst survival rates of all cancers. The bone marrow microenvironment is increasingly being recognised as an important mediator of AML chemoresistance and relapse, supporting leukaemia stem cell survival through interactions among stromal, haematopoietic progenitor and leukaemic cells. Traditional therapies targeting leukaemic cells have failed to improve long term survival rates, and as such, the bone marrow niche has become a promising new source of potential therapeutic targets, particularly for relapsed and refractory AML. This review briefly discusses the role of the bone marrow microenvironment in AML development and progression, and as a source of novel therapeutic targets for AML. The main focus of this review is on drugs that modulate/target this bone marrow microenvironment and have been examined in in vivo models or clinically.
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Chatterjee, T., GS Chowdhary, R. Singh, V. Srinivas, S. Bandyopadhyay, VK Kataria et KP Anand. « Acute Myeloid Leukaemia : AML M0 with 11q deletion ». Medical Journal Armed Forces India 64, no 2 (avril 2008) : 179–80. http://dx.doi.org/10.1016/s0377-1237(08)80075-5.
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Stalfelt, Ann Marie, Håkan Brodin, Solveig Pettersson et Anna Eklöf. « The final phase in acute myeloid leukaemia (AML) ». Leukemia Research 27, no 6 (juin 2003) : 481–88. http://dx.doi.org/10.1016/s0145-2126(02)00262-x.
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Bacher, Ulrike, Alexander Kohlmann, Claudia Haferlach et Torsten Haferlach. « Gene expression profiling in acute myeloid leukaemia (AML) ». Best Practice & ; Research Clinical Haematology 22, no 2 (juin 2009) : 169–80. http://dx.doi.org/10.1016/j.beha.2009.04.003.
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Azad, Abul Kalam, Md Rafiquzzaman Khan, ABM Hasan Habib, Md Abdul Wadud Miah et Masuda Begum. « Aberrant Expression of CD Markers in Acute Myeloid Leukaemia ». Haematology Journal of Bangladesh 2, no 01 (28 janvier 2018) : 14–16. http://dx.doi.org/10.37545/haematoljbd201812.
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Background: Aberrant expression of cluster differentiation (CD) antigen marker is associated with poor outcome of acute leukaemia. Objective: Aim of this study is to determine the frequency and pattern of aberrant expression of CD markers in acute myeloid leukaemia patients in Bangladesh. Methods: This retrospective data analysis was conducted in the Department of Haematology, Bangabandhu Sheikh Mujib Medical University (BSMMU) to assess the frequency of aberrant CD antigen expression in acute myeloid leukaemia from October 2016 to September 2017. During this period, we did one hundred flow cytometry of acute leukaemia patients and among them we found 48 acute myeloid Leukaemia (AML) who were included in this study. Result: Mean age of patients was 35 years (SD +14 years; Rang 3 to 50 years) with male: female ratio of 0.92. Four colour flow cytometry was done on fresh bone marrow aspirates and peripheral blood. Among 48 AML patients, aberrant CD expression was observed in 58% cases. CD5 and cCD79a lymphoid markers were seen to be expressed in 32% cases of AML. Aberrant cCD3 and CD7 were expressed in 29% and 25% cases respectively and aberrant CD10, CD19, cCD22 were expressed in 11%, 3%, 3% cases acute myeloid leukaemia patients respectively. Conclusion: Aberrant CD antigen expression is not uncommon in AML patients of Bangladeshi population that may adversely affect the treatment outcome of the disease.
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Onoja, AM, SA Otene, AT Onoja, IN Ibrahim, A. Mke, I. Okolie, R. Okoli et al. « Prevalence and Nature of Adult Hematological Malignancies Using Bone Marrow Aspiration Cytology in a Tertiary Health Facility : A Seven Year Retrospective Review ». Western Journal of Medical and Biomedical Sciences 2, no 1 (12 avril 2021) : 39–45. http://dx.doi.org/10.46912/wjmbs.39.
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Bone Marrow Aspiration (BMA) is a procedure that is often used to evaluate patients with haematological disorders including haematological malignancies (HMs) which account for about 6.5% of all cancers worldwide. There is paucity of data on the prevalence and pattern of HMs from BMA cytology in Nigeria. We carried out a retrospective review to determine the prevalence and distribution of HMs among adult patients who had BMA cytology at Benue State University Teaching Hospital (BSUTH) from June 2012 to July 2019. A total of 158 BMA reports extracted from the marrow and clinic medical records were reviewed. Out of 158 adult BMA cytology reports, HMs accounted for 78(49.4%) of all haematological disorders. There was no significant gender difference. The Male 38(48.7%) to Female 40(51.3%) ratio (M:F) was 1:1.1. Their ages ranged from 16 to 85 years with the median age of 54.0 years. Out of the 78 HMs, Lymphoid neoplasms were the most prevalent 47(60.3%), the leukaemias were higher 53/78(67.9%) compared to the non-leukaemic neoplasms. Of the 53 leukaemias, those of chronic lymphoid types were more 24/53(45.3%), followed by the chronic myeloid 15/53(28.3%). Chronic lymphocytic leukaemia (CLL) was the predominant leukaemia 24/53(45.3%) as well as the most prevalent HM 24/78(30.8%), followed by chronic myeloid leukaemia (CML) 19.2%(15/78). Others were myelodysplastic syndrome (MDS) 11.5%(9/78), acute lymphoblastic leukaemia (ALL) 10.3% (8/78), multiple myeloma (MM) 10.3%(8/78), acute myeloblastic leukaemia (AML) 7.7%(6/78), non-Hodgkin's lymphoma (NHL) 6.4%(5/78), Small lymphocytic lymphoma (SLL) 2.6%(2/78) and Hodgkin's lymphoma (HL) 1.3%(1/78). In conclusion, we established high prevalence of HMs among patients who had BMA cytology evaluation at BSUTH with the preponderance of lymphoid malignancies. We advocate for inclusion of HMs in the National Health Insurance Scheme (NHIS) for full implementation and to prioritise provision of modern diagnostic equipment and treatment options for quality and optimal management of leukaemias in the center.
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Walsby, Elisabeth J., Amanda F. Gilkes, Valerie Walsh, Kenneth I. Mills et Alan K. Burnett. « Hsp90 Expression in Acute Myeloid Leukaemia. » Blood 104, no 11 (16 novembre 2004) : 4471. http://dx.doi.org/10.1182/blood.v104.11.4471.4471.
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Abstract Heat shock protein inhibitors are a potential new class of anti-leukaemic agents with FLT-3 inhibitory activity. 17-allylamino-17-demethoxygeldanamycin (17-AAG) targets Hsp90 which functions as a molecular chaperone protein that promotes folding of nascent and stress denatured proteins helping them to achieve the correct conformation or targeting them for degradation. Hsp90 conformation is altered by binding ATP to a hydrophobic N-terminal pocket leading to hydrolysis which allows the protein to interact with a co-chaperone complex. 17-AAG fills the ATP binding pocket, displacing the nucleotide and inhibiting the function of Hsp90 as a chaperone. 17-AAG may affect signal transduction resulting from client proteins such as p53, c-Raf-1, Akt, Bcr-Abl and FLT-3. The level of expression of Hsp90 in AML is unknown. To examine the expression 252 AML cases and 9 normal samples were assessed by U133A GeneChips with the data analysed by MAS5 and GeneSpring 6.2.1 to give normalised gene expression of Hsp90α and β, a subset of which were then validated by real-time quantitative RT-PCR. The normalised expression range of Hspα was 0.132 to 2.727 with a mean of 0.982 (n=252) which was not significantly different from normal (0.876: n=9). Hsp90α expression was not significantly different in FAB groups, cytogenetic risk group, FLT-3 status overall or within cytogenetic risk groups. The expression of Hsp90β in the AML samples (n=252) (0.959: range 0.171 to 3.397) was not different from normal samples (0.944: range 0.535 to 1.095). However the APL subgroup (M3) (n=31) had a lower expression (0.722) than the other FAB groups (M0, M1, M2, M4, M5, M6, M7) p=0.029. There was no difference within other FAB subgroups. Apart from the influence of the t(15;17) subgroup expression levels did not vary significantly in the cytogenetic risk groups, or with the presence of a FLT-3 mutation overall or within cytogenetic risk groups. Conclusion: Hsp90 isoform expression in AML is variable over a 21 fold range. Expression does not correlate with FAB, cytogenetic risk group or FLT-3 mutation status. The relationship to clinical outcome is currently being analysed.
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Almosailleakh, Marwa, et Juerg Schwaller. « Murine Models of Acute Myeloid Leukaemia ». International Journal of Molecular Sciences 20, no 2 (21 janvier 2019) : 453. http://dx.doi.org/10.3390/ijms20020453.
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Acute myeloid leukaemia (AML) is a rare but severe form of human cancer that results from a limited number of functionally cooperating genetic abnormalities leading to uncontrolled proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Before the identification of genetic driver lesions, chemically, irradiation or viral infection-induced mouse leukaemia models provided platforms to test novel chemotherapeutics. Later, transgenic mouse models were established to test the in vivo transforming potential of newly cloned fusion genes and genetic aberrations detected in patients’ genomes. Hereby researchers constitutively or conditionally expressed the respective gene in the germline of the mouse or reconstituted the hematopoietic system of lethally irradiated mice with bone marrow virally expressing the mutation of interest. More recently, immune deficient mice have been explored to study patient-derived human AML cells in vivo. Unfortunately, although complementary to each other, none of the currently available strategies faithfully model the initiation and progression of the human disease. Nevertheless, fast advances in the fields of next generation sequencing, molecular technology and bioengineering are continuously contributing to the generation of better mouse models. Here we review the most important AML mouse models of each category, briefly describe their advantages and limitations and show how they have contributed to our understanding of the biology and to the development of novel therapies.
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Armenteros-Monterroso, Elena, Lu Zhao, Jasper de Boer et Owen Williams. « Targeting Reptin Function in Acute Myeloid Leukaemia ». Blood 126, no 23 (3 décembre 2015) : 4824. http://dx.doi.org/10.1182/blood.v126.23.4824.4824.
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Abstract Acute myeloid leukaemia (AML) is characterized by the rapid growth of immature white blood cells, which accumulate in the bone marrow and are not able to differentiate into normal functioning cells. Despite recent advances in AML therapy, cytogenetically defined subgroups with poor prognosis are still prevalent. Chromosomal translocations, which encode abnormal fusion proteins, are common in patients with AML, and the MLL (Mixed Lineage Leukaemia) locus is the most frequently rearranged in paediatric AML. Previous studies in our laboratory used global gene expression analysis in conditionally immortalized MLL-rearranged mouse myeloid cells to demonstrate that the Reptin gene was positively regulated by MLL-fusion genes. Reptin (also known as RUVBL2), together with its related family member Pontin (also known as RUVBL1), functions as part of multi-protein complexes involved in chromatin remodelling, DNA repair, regulation of transcription and ribonucleoprotein assembly. Further work in our laboratory found Reptin to be essential for sustaining the hyperproliferative state and clonogenic potential, as well as suppressing apoptosis, of human AML cells, both MLL-rearranged and non-MLL rearranged. Here, we present our recent data, investigating the transcriptional pathways regulated by Reptin in order to identify clinically approved drugs that can modulate these pathways, and using xenotransplantation assays to establish the efficacy of targeting Reptin in vivo. Our preliminary results indicate that Reptin regulates the function of the oncoprotein c-MYC in human AML cell lines and represents an exciting novel candidate target for the therapy of human AML. Disclosures No relevant conflicts of interest to declare.
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Sillar, Jonathan R., et Anoop K. Enjeti. « Targeting Apoptotic Pathways in Acute Myeloid Leukaemia ». Cancers 11, no 11 (26 octobre 2019) : 1660. http://dx.doi.org/10.3390/cancers11111660.
Texte intégralRésumé :
Acute Myeloid Leukaemia is a devastating disease that continues to have a poor outcome for the majority of patients. In recent years, however, a number of drugs have received FDA approval, following on from successful clinical trial results. This parallels the characterization of the molecular landscape of Acute Myeloid Leukaemia (AML) over the last decade, which has led to the development of drugs targeting newly identified recurring mutations. In addition, basic biological research into the pathobiology of AML has identified aberrant programmed cell death pathways in AML. Following on from successful outcomes in lymphoid malignancies, drugs targeting the B Cell Lymphoma 2 (BCL-2) family of anti-apoptotic proteins have been explored in AML. In this review, we will outline the preclinical and clinical work to date supporting the role of drugs targeting BCL-2, with Venetoclax being the most advanced to date. We will also highlight rationale combinations using Venetoclax, ongoing clinical trials and biomarkers of response identified from the early phase clinical trials performed.
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Lam, Stephen S. Y., et Anskar Y. H. Leung. « Overcoming Resistance to FLT3 Inhibitors in the Treatment of FLT3-Mutated AML ». International Journal of Molecular Sciences 21, no 4 (24 février 2020) : 1537. http://dx.doi.org/10.3390/ijms21041537.
Texte intégralRésumé :
Acute myeloid leukaemia (AML) carrying internal tandem duplication (ITD) of Fms-Like Tyrosine kinase 3 (FLT3) gene is associated with high risk of relapse and poor clinical outcome upon treatment with conventional chemotherapy. FLT3 inhibitors have been approved for the treatment of this AML subtype but leukaemia relapse remains to be a major cause of treatment failure. Mechanisms of drug resistance have been proposed, including evolution of resistant leukaemic clones; adaptive cellular mechanisms and a protective leukaemic microenvironment. These models have provided important leads that may inform design of clinical trials. Clinically, FLT3 inhibitors in combination with conventional chemotherapy as induction treatment for fit patients; with low-intensity treatment as salvage treatment or induction for unfit patients as well as maintenance treatment with FLT3 inhibitors post HSCT hold promise to improve survival in this AML subtype.
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Zhao, Chen, Aili Dai, Ling Chen, Xiaoping Sun, Xin Han, C. Cameron Yin et M. James You. « Epigenetic Inactivation of DBC1 in Acute Myeloid Leukaemia. » Blood 114, no 22 (20 novembre 2009) : 4429. http://dx.doi.org/10.1182/blood.v114.22.4429.4429.
Texte intégralRésumé :
Abstract Abstract 4429 DNA hypermethylation has important implications in the tumorigenesis and prognosis in acute myeloid leukemia (AML). To identify relevant methylated genes in AML, we have compared several expression and methylation profilings. With expression analysis, we identified that TRPC6, DBC1, DCC and SOX9 have decreased expression levels in the most analyzed AML cell lines. Among these candidates, DBC1 (deleted bladder cancer 1), a putative tumor suppressor, drew our attention because it is frequently methylated not only in hematological malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and acute lymphoblastic leukemia, but also in epithelial cancers. DBC1 may play an important role in the regulation of cell growth and programmed cell death. But the mechanisms of transcriptional control and function role in the hematological malignancies, especially on acute myeloid leukemia, are not well known. In this study, we analyzed the DBC1 expression pattern in 9 AML cell lines with RT-PCR analysis. DBC1 mRNA expression was observed in normal bone-marrow but diminished expression in all of 9 AML cell lines. DBC1 methylation was frequently observed in AML cells (9 of 9, 100%) and inversely correlated with DBC1 mRNA expression in a COBRA analysis (Combined Bisulfite Restriction Analysis). We also detected a frequent methylation of DBC1 in primary AML patient samples (9 of 9, 100%). These findings indicate that DBC1 is frequently silenced by hypermethylation in AML. We are in the process of investigation the functional role of DBC1 in the pathogenesis. In addition, diagnostic and prognostic values of DBC1 in AML are being pursued.* Chen Zhao and Aili Dai contributed equally to the presented work. Disclosures: No relevant conflicts of interest to declare.
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Kohli, Sunita, Mark Lee et Scott Marshall. « A Case Report on the Progression of Myeloid Sarcoma to Form Multiple Metastatic Deposits without Developing Acute Myeloid Leukaemia ». Case Reports in Hematology 2015 (30 septembre 2015) : 1–5. http://dx.doi.org/10.1155/2015/162154.
Texte intégralRésumé :
Introduction. Myeloid sarcomas (MS) are rare tumours occurring at extramedullary sites. They are usually associated with other haematology disorders such as acute myeloid leukaemia, myelodysplastic syndrome, and chronic myeloproliferative neoplasms. They frequently occur with a diagnosis of acute myeloid leukaemia (AML) or with relapse of preexisting disease. Patients with myeloid sarcomas without history or evidence of myeloid leukaemia typically progress to form AML. Case Presentation. A case report of a patient diagnosed with an isolated myeloid sarcoma that rarely did not transform to AML but instead spread to form multiple myeloid sarcomas throughout the body. Discussion. This case identifies the risk of metastatic spread of these tumours rather than the development of AML which is poorly documented in the literature, due to the rarity of cases, and may be significant in the investigation and management of isolated myeloid sarcomas. This case highlights the need for clinicians to consider repeat cross-sectional imaging to investigate unexplained clinical decline or symptoms, when there is no sign of AML progression and to consider radiotherapy treatment early.
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Fitzgibbon, Jude, Matthew Smith, Jamie Cavenagh et T. Andrew Lister. « Mutation of CEBPA in Familial Acute Myeloid Leukaemia. » Blood 104, no 11 (16 novembre 2004) : 2012. http://dx.doi.org/10.1182/blood.v104.11.2012.2012.
Texte intégralRésumé :
Abstract Two siblings (III-1 and III-5) were referred to St Bartholomew’s Hospital for treatment for Acute Myeloid Leukaemia (AML) within the space of 2 weeks. There was a family history of AML (see figure) occurring in their father (II-3). All other family members were alive and well. Patient II-3 was diagnosed with AML in September 1963, aged 10, patient III-1 presented in February 2003, aged 30 and his sister Patient III-5, aged 18 the following week. A diagnosis of AML FAB type M2Eo was made for both III-1 and III-5 and cytogenetic evaluation was normal. Following the diagnosis, patients III-1 and III-5 received 4 courses of combination chemotherapy. Both achieved a complete remission after the first course of therapy and both presented soon after discharge following their final course of therapy with arthralgias, fever and malaise. At that time both patients had raised white counts (28.2 x 109/l and 20.4 x 109/l respectively) in the absence of overt sepsis and off G-CSF. The abnormalities in both patients resolved without medical intervention. At the time of writing, both patients are well with normal blood counts over 17 months from diagnosis. Patient III-1 was shown to have a del (C) mutation in CEBPA at nucleotide 212 in DNA extracted from a peripheral blood sample taken at diagnosis. The corresponding protein, S21fsX158, is predicted to terminate prematurely at codon 158. III-5 was also noted to have an identical del (C) mutation in her diagnostic sample. DNA extracted from their remission peripheral blood samples and germline DNA from buccal swabs, from all 3 affected individuals, further demonstrated the presence of the del(C) 212 mutation. In this family the CEBPA mutation appears to be fully penetrant: AML developed in all carriers of the 212 del(C) mutation, identified. The long latency period (10 years - II-3, 18 years - III-5 and 30 years - III-1) suggests that one or more additional mutations is necessary for the development of overt acute leukaemia. Mutation analysis was extended to include several other genes implicated in the development of AML (KRAS, NRAS, KIT, PTPN11, FLT3 and RUNX1), but no mutations were identified other than a second CEBPA mutation (duplication of nucleotides 1050 to 1085) on the other allele in patient III-1. Direct sequencing of CEBPA from DNA extracted from peripheral blood mononuclear cells from seven healthy family members (including II-1, II-2, III-2 and III-3) confirmed the presence of wild-type sequence in each case. In summary this study describes a family with familial CEBPA mutation associated with AML and having a putative regeneration syndrome following completion of therapy. All 3 affected individuals had been previously well with no prior medical history and no obvious dysmorphism. CEBPA mutation did not therefore appear to be part of a syndrome, such as FPD/AML seen with RUNX1 mutation. However, the resultant leukaemias did appear to be similar with myeloblastic morphology, normal cytogenetics, aberrant CD7 expression and the presence of Auer rods. This observation may enable other kindreds with similar phenotype to be selectably screened for CEBPA mutation. Figure Figure
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Patterson, Shaun D., Xu Huang, Heather G. Jørgensen et Alison M. Michie. « Transcriptional Regulation by the NFAT Family in Acute Myeloid Leukaemia ». Hemato 2, no 3 (27 août 2021) : 556–71. http://dx.doi.org/10.3390/hemato2030035.
Texte intégralRésumé :
Acute myeloid leukaemia (AML) is a haematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterised as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukaemia. Furthermore, gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.
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Vey, Norbert, et Daniel Olive. « Anti-natural Killer Inhibitory Receptors in Elderly Patients with Acute Myeloid Leukaemia ». European Oncology & ; Haematology 06, no 01 (2010) : 86. http://dx.doi.org/10.17925/eoh.2010.06.1.86.
Texte intégralRésumé :
Treatment with anti-killer-cell immunoglobulin-like receptor (KIR) monoclonal antibody (mAb) is a new approach aimed at harnessing the antileukaemic potential of natural killer (NK) cells for the treatment of acute myeloid leukaemia (AML). NK cell antitumour activity is regulated by a balance between activating and inhibitory receptors (KIR). 1-7F9/IPH2101 is a fully human immunoglobulin G4 (IgG4) mAb that binds to inhibitory KIR and blocks binding with its ligand (human leukocyte antigen C [HLA-C] molecule) on leukaemic cells.In vitro,and in a surrogatein vivomodel in mice, treatment with 1-7F9/IPH2101 was able to induce NK cell activation and cytotoxicity against leukaemic cells. Patients with AML often display abnormal NK cell function, while evidence of an impact of NK cell status on AML outcome has been reported in allogeneic transplantation. 1-7F9/IPH2101 is currently under clinical investigation in patients with AML. This article reviews the mechanisms of NK cell antileukaemic activity and its role and defects in AML. Currently available data on the pre-clinical and clinical development of 1-7F9/IPH2101 are presented, and the rationale for its future use as a single agent or in combination is discussed.
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Büchner, Thomas, Wolfgang Hiddemann, Claudia Schoch, Torsten Haferlach, Maria-Cristina Sauerland et Achim Heinecke. « Acute myeloid leukaemia (AML) : treatment of the older patient ». Best Practice & ; Research Clinical Haematology 14, no 1 (mars 2001) : 139–51. http://dx.doi.org/10.1053/beha.2000.0120.
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Davis, Julian R., David J. Benjamin et Brian A. Jonas. « New and emerging therapies for acute myeloid leukaemia ». Journal of Investigative Medicine 66, no 8 (19 août 2018) : 1088–95. http://dx.doi.org/10.1136/jim-2018-000807.
Texte intégralRésumé :
The treatment of acute myeloid leukemia (AML) has remained relatively unchanged for the past 3–4 decades with generally poor outcomes, especially in elderly populations unfit for intensive therapy. Recent advancements, however, have identified several cytogenetic and molecular markers that have not only improved prognostication but have also led to the development of several new targeted therapies for specific subpopulations. In 2017, the US Food and Drug Administration approved four new treatments with indications for fms like tyrosine kinase 3 (FLT3)-mutated AML (midostaurin), newly diagnosed or relapsed/refractory CD33+AML (gemtuzumab ozogamicin), newly diagnosed therapy-related AML or AML with myelodysplasia-related changes (CPX-351) and relapsed/refractory AML with an isocitrate dehydrogenase (IDH)2 mutation (enasidenib). These newly approved therapies have demonstrated improved response in their target populations in several pivotal clinical trials with some also demonstrating improved overall survival. Additional novel therapies in development for AML include agents that target B cell lymphoma 2, FLT3, IDH1, the ubiquitination pathway, as well as cell therapy using engineered T cells with chimeric antigen receptors. This review provides a summary of the four newly approved therapies for AML, as well as several promising therapies currently in development.
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Kavanagh, Simon, Bob Mirzai, Kathy Fuller et Wendy N. Erber. « TGFα expression in myeloid malignancies ». Journal of Clinical Pathology 69, no 6 (16 mars 2016) : 543–46. http://dx.doi.org/10.1136/jclinpath-2015-203526.
Texte intégralRésumé :
BackgroundTransforming growth factor α (TGFα) is a peptide growth factor known to be expressed in normal haemopoiesis. It is also expressed in a range of epithelial neoplasms but has not been assessed in haemopoietic malignancies. We have performed an immunohistochemical evaluation of TGFα in acute and chronic myeloid malignancies.MethodsTGFα expression was semiquantitatively assessed in 69 normal bone marrow trephines and 157 cases of myeloid malignancy using an immunohistochemical approach.ResultsBlast cells of myeloid origin in acute myeloid leukaemia (AML), myelodysplasia and accelerated and blast phases of chronic myeloid leukaemia (CML) were TGFα positive. In acute promyelocytic leukaemia the neoplastic cells had significantly weaker TGFα expression than seen in other forms of AML. The blast cells in CML-accelerated and blast phases were positive with similar expression to AML.ConclusionsTGFα is expressed in neoplastic myeloblasts and could, therefore, be used as blast cell biomarker in diagnostic haematopathology. In addition, TGFα immunohistochemistry may be of use in identifying a therapeutic target.
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Dachi. « Acute Leukaemias in Bauchi State, Northeastern Nigeria : Pattern of Presentations and Clinical Entities ». West Africa Journal of Medicine 39, no 5 (26 juin 2022) : 497–500. http://dx.doi.org/10.55891/wajm.v39i5.122.
Texte intégralRésumé :
Background: Acute leukaemias are very aggressive diseases that run a rapidly fatal course if not promptly diagnosed and appropriately treated. The clinical presentations range from bone marrow failure such as anaemia, neutropenia or thrombocytopenia to features of organ infiltrations such as lymphadenopathy, splenomegaly, etc, but presentations may be non-specific. Misdiagnosis is very common with delay in diagnosis and prompt treatment being the causes of high morbidity and mortality in acute leukaemias. This study aims to determine the pattern of presentation and various clinical entities of acute leukaemias in Bauchi State, North-Eastern Nigeria.
Subjects, materials and methods: This was a three year retrospective study in which records of cases of acute leukaemias diagnosed in the Haematology Department of Abubakar Tafawa Balewa University Teaching Hospital (ATBUTH) Bauchi from the bone marrow aspiration cytology register from 1st January, 2018 to 31st December, 2020 were collected. Data on socio-demographic characteristics of the patients that include age, gender, diagnosis as well as subtypes of some of the malignancies diagnosed were also collated. The collated data were analyzed using SPSS Version 20.0. A p-value of < 0.05 was considered significant.
Results: Twenty-nine cases of acute leukaemias were diagnosed during the period under review. Majority of cases had acute lymphoblastic leukaemia (ALL) 19/29 (65.5%) while acute myeloid leukaemia (AML) was seen in 10/29 (34.5%). The mean ± SD age of the patients was 22.2±9.2 years with a range 6 months to 60 years. Males constituted 75.9% (22/29) of the cases of acute leukaemias diagnosed. The male to female ratios for AML and ALL were 2:1 and 2.6:1 respectively. The mean±SD ages for AML and ALL were 27±9.2years and 17.3±11.3 years respectively. The most common form of presentation of acute leukaemia in this study is recurrent anaemia necessitating blood transfusion while proptosis and epistaxis were the least forms of presentation.
Conclusion: Acute lymphoblastic leukaemia is the commonest form of acute leukaemias while recurrent anaemia is the commonest form of clinical presentations in our setting. Early referral of patients with clinical features suggestive of acute leukaemias is recommended.
Author
R A Dachi 1, F G Mustapha 1, M Mahdi 1, H Abbas 2
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BEGHDOUD, Sara Khedidja, Chahrazed YOUCEF, Mustapha DIAF et Amaria BOUMEDANE. « COMPARISON OF CLINICAL, BIOLOGICAL AND EVOLUTIONARY CHARACTERISTICS BETWEEN CHILDHOOD ACUTE LYMPHOBLASTIC AND MYELOID LEUKEMIA IN WESTERN ALGERIA, FROM 2016 TO 2018 ». Journal of Drug Delivery and Therapeutics 10, no 4 (15 juillet 2020) : 1–7. http://dx.doi.org/10.22270/jddt.v10i4.4202.
Texte intégralRésumé :
Background and Objectives: Haematological malignancies account for approximately 40% of all cancers by the age of 15 years. Acute leukaemia (AL) account for one-third of childhood cancer cases; consisting of Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML). The aim of this work is to describe the epidemiological, clinical, biological and evolutionary characteristics of children with acute leukaemia in the western and south-western region of Algeria.
Patients and Methods: A three-year retrospective study was undergone from January 2016 to December 2018 on children with acute leukaemia. The study was conducted at the paediatric oncology department of the anti-cancer -Emir AEK- of Missreghine in Oran.
Results: During this period, we identified 135 cases of diagnosed AL. The sex ratio M/F was 1.1. The “two to five-year” age group was the most affected. The prevalence of ALL, AML, and biphenotypic acute leukaemia (BAL) was 60.45%, 23.88%, and 15.57%, respectively. The clinical signs were mainly presented by the tumour syndrome dominated by the presence of lymphadenopathy (63%) and splenomegaly (56.3%). The most frequent abnormal blood abnormalities were anaemia (66.66% in ALL and 28.14% in AML), thrombocytopenia (75.9% in ALL and 24.4% in AML) and leukocytosis (76.3% ALL and 23.7% AML).
Conclusion: Paediatric acute leukaemia is a real public health problem that requires special care and attention. This management must involve all epidemiological, clinical and biological aspects for this highly sensitive age group.
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Troke, Philip J. F., Karin B. Kindle, Hilary M. Collins et David M. Heery. « MOZ fusion proteins in acute myeloid leukaemia ». Biochemical Society Symposia 73 (1 janvier 2006) : 23–39. http://dx.doi.org/10.1042/bss0730023.
Texte intégralRésumé :
MOZ (monocytic leukaemia zinc finger protein; also known as ZNF220 or MYST3) is a member of the MYST family of protein acetyltransferases. Chromosomal translocations involving the MOZ gene are associated with AML (acute myeloid leukaemia), suggesting that it has a role in haematopoiesis. Recurrent reciprocal translocations fuse the MOZ gene [or the gene encoding MORF (MOZ-related factor); also known as MYST4] to genes encoding the nuclear receptor co-activators CBP [CREB (cAMP response element-binding protein)-binding protein], p300 or the p160 protein TIF2 (transcription intermediary factor 2). The resulting fusion proteins can transform haematopoietic progenitors in vitro, and induce myeloproliferative disease in mice. Recent insights into the molecular mechanisms underlying these effects indicate that MOZ fusion proteins interfere with the activities of transcription factors such as nuclear receptors, p53 and Runx proteins. Our studies suggest that subverting the function of cellular CBP and p300 proteins may play a key role in this process. Here we review the recent progress in understanding the role of MOZ fusion proteins in the aetiology of AML.
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Elsissy, Maha, Ahmed Abdelhafez, Manal Elmasry et Doaa Salah. « Interleukin-17 Gene Polymorphism Is Protective Against the Susceptibility to Adult Acute Myeloid Leukaemia in Egypt : A Case-Control Study ». Open Access Macedonian Journal of Medical Sciences 7, no 9 (15 mai 2019) : 1425–29. http://dx.doi.org/10.3889/oamjms.2019.306.
Texte intégralRésumé :
BACKGROUND: Th17 cells are blamed for being accused in the pathogenesis of acute myeloid leukaemia. Th17 cells are CD4+ cell subtype. They produce IL-17A and IL-17F.
AIM: This study aims to trace the relation between IL-17A and IL-17F polymorphisms and AML incidence and to define the connection between IL-17 polymorphisms and its serum level.
METHODS: A group of 100 acute myeloid leukaemia patients and 100 age and sex-matched healthy subjects (controls) were enrolled in the present work. Restriction fragment length polymorphism- polymerase chain reaction (PCR-RFLP) was done to detect IL-17A (rs2275913; G197A) and IL-17F (rs763780; A7488G). Serum IL-17 level was assessed by Enzyme-linked immunosorbent assay analysis (ELISA) in both patients and controls.
RESULTS: IL-17F, IL-17A mutant genotypes and alleles showed no significant relation with acute myeloid leukaemia incidence. Also, ELISA results proved that serum IL-17 did not vary between acute myeloid leukaemia patients and healthy subjects.
CONCLUSION: Interleukin-17 gene polymorphisms did not consider a risk for acute myeloid leukaemia.
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Kapelko-Slowik, Katarzyna, Donata Urbaniak-Kujda, Dariusz Wolowiec, Jaroslaw Dybko, Bozena Jazwiec, Miroslaw Slowik, Jacek Jakubaszko, Tomasz Owczarek, Krzysztof Grzymajlo et Kazimierz Kuliczkowski. « Expression of PIM-2 and NF-κB Is Increased in Patients with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) and Correlates with Complete Remission Rate ». Blood 118, no 21 (18 novembre 2011) : 4648. http://dx.doi.org/10.1182/blood.v118.21.4648.4648.
Texte intégralRésumé :
Abstract Abstract 4648 Background. PIM-2 is a proto-oncogene that encodes for serine/threonine kinase which interacts with various signalling molecules. PIM-2 is highly expressed in neoplastic tissues and in leukaemic and lymphoma cell lines which is consistent with a its role during oncogenic transformation. The nuclear factor kappa B (NF-κB) pathway appears to be deregulated in variety of tumors, with sustained activity of NF-κB leading to apoptotic resistance in tumor cells The aim. The aim of this study was to investigate whether the PIM-2 and NF-κB expression is altered in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Patients and methods. One hundred fourty-three patients were included: 91 with AML and 52 with ALL (42 with B-ALL and 10 with T-ALL), aged 18–84 (median=41). Seventy-five patients reached complete remission (CR): 50 in AML and 25 in ALL. Bone marrow samples were collected at the time of diagnosis. Control samples were obtained from 24 healthy donors. We analysed PIM-2 and NF-κB expression by RQ-PCR analysis. Results. Expression of both PIM-2 and NF-κB in all leukaemic patients and in subgroups: AML and ALL was significantly higher than in controls. In AML group patients who reached CR expressed PIM-2 and NF-κB at significantly lower levels than patients with primary resistance to chemotherapy (with no CR, NCR). Moreover in AML, we have found the correlation between PIM-2, NF-κB expression and blasts in myelogram and PIM-2 and patients‘ age. Summary. Our data indicate that PIM-2 and NF-κB genes expression is increased in patients with AML and ALL and correlates with CR rate in AML patients. Disclosures: No relevant conflicts of interest to declare.
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Goh, Sal Lee, Jean-Pierre Levesque, Allison R. Petitt, Valarie Barbier et Ingrid G. Winkler. « Therapeutic Blockade of Macrophage Colony Stimulating Factor (CSF-1) Delays AML Progression in Mice In Vivo ». Blood 128, no 22 (2 décembre 2016) : 2835. http://dx.doi.org/10.1182/blood.v128.22.2835.2835.
Texte intégralRésumé :
Abstract Macrophage colony-stimulating factor (M-CSF or CSF-1) plays a role in regulating innate immune responses promoting macrophage growth and differentiation. We hypothesized CSF-1 may also play a role in growth and progression of Acute Myeloid Leukaemia (AML). The aim of this study is to investigate the role of CSF-1 in survival and chemo-resistance of leukaemia stem and progenitor cells (LSPC). We further hypothesized that blocking CSF-1R signalling in LSPC may dampen leukaemia survival in vitro and delay leukaemia progression in vivo. AML was induced in mice by injecting murine Haematopoietic Stem and Progenitor Cells (HSPC) transduced with either MLL-AF9 or AML1- ETO fusion oncogenes for the development of either monomyelocytic or granulocytic leukaemia respectively. We found CSF-1R, the main receptor for CSF-1, was expressed on these acute myeloid leukaemia cells, thus it is possible that CSF-1 provide supportive microenvironment for leukemic growth. To identify whether CSF-1 in the bone marrow (BM) niche is essential for growth of malignant LSPC, we harvested normal or- leukaemic blasts from BM for in vitro studies using Long-Term Culture-Initiating-Cell (LT-CIC) assays. In these assays AML LSPC or normal HSPC cells were co-cultured with mesenchymal stromal cells (MSC) from either wildtype mice (MSC that produce CSF-1) or MSC from OP/OP mice (unable to produce functional CSF-1). We found normal (wild-type) HSPC were able to proliferate, survive and produce LT-CIC in the absence of niche-provided CSF-1, however AML blasts could not, unless rescued by addition of recombinant CSF-1 (100 ng/mL) in vitro. Together these data suggest CSF-1 signalling may be critical for AML LSPC but not normal HSPC. Next we investigated in mice whether therapeutic CSF-1 blockade could similarly dampen AML survival or progression in vivo. Cohorts of mice were injected with luciferase-expressing monomyelocytic (MLL-AF9) BM leukaemic blasts, then 7 days later administered the small molecule CSF-1 antagonist (GW2580, 160mg/kg daily for 10 days) or vehicle control. Leukaemia progression was tracked by biweekly bioluminescence and testbleeds for appearance of GFP+ leukaemia blasts in blood. We found therapeutic blockade of CSF-1 significantly reduced tumour burden in these mice by both bioluminescence and testbleed analysis. Mice were also monitored for duration of survival. As anticipated by the observed reduction in leukaemia burden, therapeutic CSF-1 blockade also significantly extended the duration of overall mouse survival (P<0.005, n= 8 mice/ group). Together these studies suggest therapeutic CSF-1 blockade may show promise as an adjunct therapy to help reduce tumour burden and improve success of AML leukaemia therapies. Disclosures Winkler: GlycoMimetics: Research Funding.
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Brown, Elliott, et Barbara-ann Guinn. « Molecular Mechanisms and Therapies of Myeloid Leukaemia ». International Journal of Molecular Sciences 23, no 11 (2 juin 2022) : 6251. http://dx.doi.org/10.3390/ijms23116251.
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Antonijevic, Nebojsa, Nada Suvajdzic, Tatjana Terzic, Branko Jakovljevic, Gradimir Jankovic, Ivo Elezovic, Rajko Milosevic et Milica Colovic. « Favourable prognostic factors in therapy related acute myeloid leukaemia ». Srpski arhiv za celokupno lekarstvo 139, no 5-6 (2011) : 347–52. http://dx.doi.org/10.2298/sarh1106347a.
Texte intégralRésumé :
Introduction. Therapy related acute myeloid leukaemia (t-AML) is a distinct clinical entity recognized by the World Health Organization classification occurring after chemotherapy and/or radiation treatment administered for a previous disease. T-AML is characterised by pancytopenia, three-lineage myelodysplasia, high frequency of unfavourable cytogenetics and short survival. Objective. The aim of this study was to analyse clinical, cytogenetic, and cytological characteristics of t-AML and their impact on survival. Methods. Seventeen patients with t-AML (8 male and 9 female; median age 59 years) were identified among 730 consecutive patients with acute myeloid leukaemia. The degree of three-lineage dysplasia as well as haematological, cytological and cytogenetic analyses, were assessed by standard methods. Results. The patients survived a median of 62.5 days with the 10% probability of survival during two years. Prognostically favourable factors were a higher percentage of dysplastic granulocytic cells, age less than 60 years, and presence of prognostically favourable karyotype inv(16), t(15;17), t(8;21). Conclusion. The stated prognostic factors that include age, cytogenetics findings and granulocytic dysplasia analysis could contribute to adequate risk stratification of t-AML, though fuller results would require additional analyses.
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Sedick, Qanita, Sultan Alotaibi, Saeed Alshieban, Khalid Ben Naheet et Ghaleb Elyamany. « Natural Killer Cell Lymphoblastic Leukaemia/Lymphoma : Case Report and Review of the Recent Literature ». Case Reports in Oncology 10, no 2 (7 juillet 2017) : 588–95. http://dx.doi.org/10.1159/000477843.
Texte intégralRésumé :
Natural killer (NK) cell lymphoblastic leukaemia/lymphoma is a rare haemopoietic tumour currently defined in the 2008 WHO classification under the category of acute leukaemias of ambiguous lineage. A diagnosis of this type of leukaemia is considered in cases expressing CD56 along with immature T-cell-associated markers such as CD2 and CD7 with absence of B-cell and myeloid markers; in addition, blastic plasmacytoid dendritic cell leukaemia should be excluded. Prior to 2008, these precursor NK cell lymphoblastic leukaemias/lymphomas were categorized as myeloid/NK cell acute leukaemia with a phenotype identical to acute myeloid leukaemia with minimal differentiation. While the new classification has merit in having excluded myeloid expression, there is still persistent confusion in the literature and on a practical level with regard to precursor NK cell neoplasms. There is a paucity of recent case reports in the literature after the new WHO classification of this neoplasm. Due to the rarity of this neoplasm, an accurate pathological diagnosis is often difficult. In this article, we describe a case of precursor NK cell lymphoblastic leukaemia/lymphoma presenting with unique morphological features and conflicting immunophenotypes. We also review all case reports of this neoplasm after the WHO 2008 classification.
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Nachbaur, David. « Acute myeloid leukaemia (AML) and allogeneic haematopoietic stem cell transplantation ». memo - Magazine of European Medical Oncology 2, no 2 (juin 2009) : 104–7. http://dx.doi.org/10.1007/s12254-009-0117-7.
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GRIGG, A., P. BARDY et J. SZER. « Allogeneic bone marrow transplantation for relapsed acute myeloid leukaemia (AML) ». Australian and New Zealand Journal of Medicine 26, no 4 (août 1996) : 570–71. http://dx.doi.org/10.1111/j.1445-5994.1996.tb00613.x.
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Mussai, Francis J., Sharon Egan, Joseph Higginbotham-Jones, Anthony Lo, Margaret Ng, Tracey A. Perry, Justin Loke et al. « Cytotoxicity of the Recombinant Human Arginase (BCT-100) Against Acute Myeloid Leukaemia (AML) ». Blood 124, no 21 (6 décembre 2014) : 2317. http://dx.doi.org/10.1182/blood.v124.21.2317.2317.
Texte intégralRésumé :
Abstract Acute Myeloid Leukaemia (AML) is one of the most common leukaemias in both adults and children however improvements in overall survival have plateaued resulting in significant numbers of patients dying of disease. A major challenge is to find new drugs which are active against AML blasts or which make blasts more sensitive to existing chemotherapy. Arginine, is a semi-essential amino acid, required for protein synthesis, and cell viability. Some cancers are dependent on arginine for proliferation and survival - ‘arginine auxotrophism’. We have recently identified that arginine metabolism plays a key role in AML pathogenesis (Mussai et al. Blood. 2013). Therefore therapeutic depletion of arginine could be an Achilles-heel in AML survival. A clinical grade, FDA approved, pegylated-recombinant human arginase, PEG-rhArgI molecule BCT-100, has been developed by Bio-Cancer Treatment International (BCT, Hong Kong). A Phase I and II clinical trial has been successfully completed in adult hepatocellular carcinoma. The Phase I trial demonstrated that at 1600U/kg BCT-100 (Observed Biological Dose), plasma arginine falls below 8mM (Adequate Arginine Depletion - ADD) and is maintained for up to 166 hours, with no evidence for neutralising immunogenicity. Only grade 1 or 2 reversible transaminitis was seen and patients experienced significant improvements in overall survival. In this study we tested the cytotoxicity of BCT-100 against AML. We demonstrated that AML cell lines (n=4) are dependent on arginine for proliferation and survival. In vitro, BCT-100 leads to a complete depletion of arginine within 8 hours at doses significantly below those achievable in humans. In AML cell lines, BCT-100 arginine depletion causes an inhibition of cell division and G0/1 phase cell cycle arrest, leading to necrotic cell death (IC50 50-225mU/ml), confirmed by flow cytometry staining and electron microscopy. NOD-SCID AML xenografts treated with BCT-100 (50mU/kg iv twice weekly for 4 weeks) had a significant reduction in AML bone marrow engraftment (p=0.05). The in vitro activity of BCT-100 was tested against primary blasts from 17 AML patients (n=14 adults, n=3 paediatric). The IC50 ranged from 85-800mU/ml in 10/15 patients. Necrotic cell death was confirmed by flow cytometry and electron microscopy. Cytotoxicity of BCT-100 is additive in combination with low dose cytarabine in vitro (p=0.002). In this small cohort, sensitivity to BCT-100 did not correlate with clinical or cytogenetic characteristics. Resistance to cytarabine does not correlate with resistance to BCT-100 (p=0.06). The enzymes OTC and ASS have been identified as biomarkers of sensitivity to arginine depletion in solid tumours. ASS and OTC expression pattern was characterised in leukaemic blasts from 30 (20 adult, 10 paediatric) AML patients, revealing the majority of AML cases are deficient in one or more of these enzymes (Adults: ASS-: 55% OTC: 34%; Paediatric: ASS- 80% OTC 20%). Importantly we demonstrated that BCT-100 is active against AML blasts expressing both ASS and OTC. RNA-sequencing of BCT-100 resistant and sensitive blasts identified a number of putative, predictive pathways involved in resistance to arginine depletion. The study is the first report on the cytotoxicity of pegylated human recombinant arginase BCT-100 against adult and paediatric AML. The data provides the rationale for an upcoming Phase I/II trial of BCT-100 for relapsed/treatment resistant AML. Disclosures No relevant conflicts of interest to declare.
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Kayser, Sabine, et Richard F. Schlenk. « Targeting the FLT3 Mutation in Acute Myeloid Leukaemia ». European Oncology & ; Haematology 13, no 02 (2017) : 139. http://dx.doi.org/10.17925/eoh.2017.13.02.139.
Texte intégralRésumé :
Acute myeloid leukaemia (AML) exhibiting an internal tandem duplication of the FLT3 gene (FLT3-ITD) is an aggressive haematologic malignancy with a poor prognosis due to a high relapse rate and very limited options after relapse with conventional salvage regimens, whereas the prognostic impact of point mutations in the tyrosine kinase domain of the FLT3 gene (FLT3-TKD) are less clear. A number of tyrosine kinase inhibitors (TKIs) have been developed that inhibit the constitutively activated kinase activity caused by the FLT3 mutation, thus interrupting signalling pathways. Early clinical trials of these agents as monotherapy failed to elicit enduring complete responses, leading to clinical testing of FLT3 TKI in combination with conventional chemotherapy. Midostaurin has demonstrated improved survival in combination with standard intensive chemotherapy as compared to standard chemotherapy alone in younger adult patients with newly diagnosed FLT3-mutated AML and is the first and currently the only approved FLT3 TKI. Newer, more selective compounds, such as gilteritinib and crenolanib, have also demonstrated significant potency and specificity. Several combination trials are ongoing or planned in both relapsed and newly diagnosed AML patients with activating FLT3 mutations.
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Zuna, Jan, Tatiana Burjanivova, Zuzana Zemanova, Sharon Horsley, Lyndal Kearney, Katerina Muzikova, Claus Meyer et al. « MLL Translocation in a Multipotent Progenitor Causing Acute Lymphoblastic Leukaemia - Two-Step Model of the Disease. » Blood 108, no 11 (1 novembre 2006) : 2295. http://dx.doi.org/10.1182/blood.v108.11.2295.2295.
Texte intégralRésumé :
Abstract Leukaemias with MLL gene rearrangement are usually considered prognostically unfavourable and the clinical symptoms typically follow the translocation formation rapidly. MLL rearrangement is thus thought to be a major hit in leukaemogenesis that is either sufficient to cause the disease or it is a very strong and rapid inducer of the subsequent hit(s) required for the malignant transformation. We report an unusual presentation of secondary acute lymphoblastic leukaemia (sALL) with MLL rearrangement. Our patient was diagnosed originally with acute myeloid leukaemia (AML-M3) characterised by PML/RARα fusion and an internal tandem duplication of FLT3 (FLT3/ITD). After 30 months of complete remission of AML, she developed sALL with MLL/FOXO3A fusion gene. Bone marrow (BM) samples taken during AML therapy were analysed for the presence of these aberrations. Both the PML/RARα fusion and FLT3/ITD disappeared shortly after AML onset and did not reappear. However, FISH and quantitative RT-PCR showed the presence of the MLL/FOXO3A fusion 20 months before the diagnosis of sALL, present in 10–90% of BM cells. Morphological examination showed no blast infiltration of the BM at this time. Experiments combining FISH and morphology confirmed the presence of an MLL rearrangement in myeloid as well as lymphoid cells, indicating that the fusion arose in a multipotent progenitor. In order to identify potential secondary genetic events precipitating sALL in this patient, we used Affymetrix 50K single nucleotide polymorphism (SNP) array analysis on DNA from the diagnostic sALL sample versus the "preleukaemic" (remission AML) sample taken 16 months before. This analysis revealed a 10 Mb amplification on 19q13.32 in the sALL sample, not present in the preleukaemic sample: this was confirmed by FISH with a BAC from the amplified region. A difference between the pre-leukaemic and leukaemic cells is also demonstrated by the incomplete rearrangement of IgH gene (DH1/JH) present only at the diagnosis of sALL. There are about 450 genes in the amplified region on 19q and several of them might be involved in deregulation of the preleukaemic cell if overrepresented (e.g. FLT3 ligand, interleukin 11, Ras interacting protein 1, Stem cell growth factor, Aurora C). The long latency period prior to the onset of the secondary leukaemia in our case resembles the mouse model of MLL/FOXO3A. However, in contrast to the animal model and also to the previous reports of MLL/FOXO3A patients (2 cases described so far, both secondary AMLs after Hodgkin’s disease), our child developed leukaemia from the lymphoid lineage. Taken together, these results indicate that the MLL/FOXO3A fusion alone is not sufficient to cause leukaemia and that second hit is required to the onset of the disease. A responsible gene is possibly located on the telomeric part of the 19q.
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Bittar, Gianfranco, Diana De Oliveira-Gomes et Gustavo Rivero. « Advances and Future Goals in Acute Myeloid Leukaemia Therapy ». Oncology & ; Haematology 18, no 2 (2022) : 130. http://dx.doi.org/10.17925/ohr.2022.18.2.130.
Texte intégralRésumé :
The treatment of acute myeloid leukaemia (AML) remains challenging, given the disease's heterogeneous genomics, epigenetics and immunology. Although novel drugs are rapidly being developed, the outcomes of patients with AML remain suboptimal, especially among individuals older than 75 years and those with primary relapsed/refractory disease. While molecular characterization can inform the use of targeted therapies, several limitations, including low response rates and short durations of remission when targeted agents are used as monotherapies, restrict the efficacy of this strategy. It is likely that combining targeted agents with either chemotherapy or hypomethylating agents will help to advance the field. Here, we review current cytogenetic and genomic European LeukemiaNet risk-stratification models for AML. We present the cases of three patients with AML that illustrate the therapeutic recommendations for patients in specific genomic subgroups, emphasizing recent results with a hypomethylating agent plus B-cell lymphoma 2 inhibitor therapy in elderly patients. Finally, we summarize data from clinical trials that promise to improve AML therapy.
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Parikh, Sameer A., et Stefan Faderl. « Clinical Management of Relapsed/Refractory Acute Myeloid Leukaemia ». European Oncology & ; Haematology 00, no 04 (2010) : 43. http://dx.doi.org/10.17925/eoh.2010.04.0.43.
Texte intégralRésumé :
Conventional chemotherapy for patients with relapsed/refractory acute myeloid leukaemia (AML) remains unsatisfactory, with median survival ranging from 18 weeks following first relapse to six weeks in those with a second or higher relapse. The only potentially curative therapy is stem cell transplantation. Duration of first complete remission (CR) is the best predictor of response to salvage therapy. Novel therapies directed against a number of molecular aberrations associated with AML are being developed, including anti-CD33 monoclonal antibodies, FMS-like tyrosine kinase (FLT3) inhibitors, nucleoside analogues, hypomethylating agents and histone deacetylatase inhibitors, among others. Clinical trials combining novel agents with conventional chemotherapy are of particular interest, and definition of dose, schedule and combination partners remains an area of intense research.
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Hangen, Hanne, Dirk Reinhard, Frank Griesinger, Lorenz Truemper, Gerburg M. Wulf et Gerald G. Wulf. « Pin1 in Acute Myeloid Leukemia Blast Cells. » Blood 106, no 11 (16 novembre 2005) : 4539. http://dx.doi.org/10.1182/blood.v106.11.4539.4539.
Texte intégralRésumé :
Abstract Pin1 is a peptidyl-prolyl-isomerase catalysing conformational changes on ser/thr-pro-sites of proteins, and has been shown to play a pivotal role for the activity of cell cycle regulating proteins in breast and prostate cancer cells. Overexpression of Pin1 has been found in many cancers, and we here present first data on its expression in blast cells of patients with acute myeloid leukaemia (AML). Having documented Pin1 expression in leukemic cell lines with highest expression levels in the promyelocytic leukemia cell line HL60, we analyzed the expression of Pin1 in bone marrow samples with high blast counts from 24 pediatric and 28 adult patients with AML by semiquantitative RT-PCR and flow cytometry. Expression levels varied considerably, ranging from undetectable in 16 of 52 cases, to very high levels of up to 13.7 units normalized on abl-expression in the RT-PCR. Pin1 levels did not correlate with patient age, nor the expression of progenitor or myeloid differentiation markers on the blast cell population. Also, Pin1 level did not segregate with FAB classification, nor the prognostic implications of cytogenetic findings. Comparing Pin1-negative to Pin1-positive leukaemia cases at a median observation time of 32 months by Kaplan-Meier analysis, we found a tendency towards better event free (p=0.01) and overall survival (p=0.058) for the Pin1-positive cases. In summary, Pin1 was found in the leukemic blast cells of most patients with AML, and further investigations on prognostic significance and function of Pin1 in AML appear warranted.
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Cairns, Lauren V., Katrina M. Lappin, Alexander Mutch, Ahlam Ali, Kyle B. Matchett et Ken I. Mills. « Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia ». International Journal of Molecular Sciences 22, no 18 (21 septembre 2021) : 10163. http://dx.doi.org/10.3390/ijms221810163.
Texte intégralRésumé :
Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.
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Agase, D. M., S. B. Zade, M. S. Markam, P. M. Mohurle, P. R. Chaudhari, S. P. Padole, P. R. Bandebuche, P. D. Bhoyar, A. D. Pangal et A. K. Ganju. « Studies on the morphology of leukaemic blast cells in relation to haematological parameters ». Journal of Applied and Natural Science 12, no 2 (31 mai 2020) : 171–79. http://dx.doi.org/10.31018/jans.vi.2267.
Texte intégralRésumé :
A combination of haematological parameters with morphological evaluation of peripheral blood and bone marrow blast cells is crucial for leukaemia diagnosis. FAB (French– American–British) classification is a simple and powerful diagnostic tool for leukaemia in developing countries like India. Differentiation block in the early stages of haematopoiesis and morphological characteristics of leukemic blast cells are directly related to haematological parameters. The present study is an approach to increase understanding of the simple morphological FAB classification of leukaemia in relation to haematological parameters. The present study revealed that Chronic Myeloid Leukaemia (CML) was the most common type of leukaemia , followed by Acute Myeloid Leukaemia, Acute Lymphoid Leukaemia (ALL), and Chronic Lymphoid Leukaemia (CLL) in Nagpur. Most of the cases of Acute Leukaemia had severe anaemia and thrombocytopenia. Highest variation was found in Total WBCs count of different types of leukaemia , particularly in different subtypes of AML. The present study also suggested that FAB classification is not outdated, but it does require continuous revalidation and other procedures for refinement.
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Ianniello, Zaira, et Alessandro Fatica. « N6-Methyladenosine Role in Acute Myeloid Leukaemia ». International Journal of Molecular Sciences 19, no 8 (9 août 2018) : 2345. http://dx.doi.org/10.3390/ijms19082345.
Texte intégralRésumé :
We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m6A), in particular, has attracted the interest of researchers all around the world. m6A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation. m6A is installed by “writers”, removed by “erasers”, and recognized by “readers”; thus, it can be compared to the reversible and dynamic epigenetic modifications in histones and DNA. Given its fundamental role in determining the way mRNAs are expressed, it comes as no surprise that alterations to m6A modifications have a deep impact in cell differentiation, normal development and human diseases. Here, we review the proteins involved in m6A modification in mammals, m6A role in gene expression and its contribution to cancer development. In particular, we will focus on acute myeloid leukaemia (AML), which provides an initial indication of how alteration in m6A modification can disrupt normal cellular differentiation and lead to cancer.