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1

Sarrou, Evgenia, Laura Richmond, Ruaidhrí J. Carmody, Brenda Gibson e 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, n. 12 (15 giugno 2020): 4266. http://dx.doi.org/10.3390/ijms21124266.

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Abstract (sommario):
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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2

Kuzmits, Rudolf, Paul Aiginger, Matthias M. Müller, Günter Steurer e Werner Linkesch. "Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells". Clinical Science 71, n. 1 (1 luglio 1986): 81–88. http://dx.doi.org/10.1042/cs0710081.

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1. A short-term test in vitro is described, which can be used to detect resistance to cytostatic agents in leukaemic cells. Leukaemic cell suspensions were incubated with cytostatic agents and the resulting intracellular ATP concentrations were measured by a bioluminescence ATP assay. 2. There was a clear dose-effect relationship in acute leukaemia and chronic lymphocytic leukaemia cells for drugs used in the treatment of leukaemias. A good correlation was found between the ATP content of leukaemic cells and cell viability as determined by the trypan blue dye exclusion test. 3. Preliminary individual clinical correlations suggest a correlation between the chemosensitivity in vitro and the response patterns in vivo in leukaemia patients. This simple, fast and sensitive method may have application for determination of drug-induced cytotoxicity in leukaemic cells in vitro.
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3

Skarsgård, Lisa Stenman, Mattias K. Andersson, Marta Persson, Ann-Cathrine Larsen, Sarah E. Coupland, Göran Stenman e Steffen Heegaard. "Clinical and genomic features of adult and paediatric acute leukaemias with ophthalmic manifestations". BMJ Open Ophthalmology 4, n. 1 (ottobre 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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4

Nurunnabi, Md, Mosammath Khadiza Mamdu, Ayesha Siddika, Farzana Zafreen, Md Abdul Wahab e Shahana Shermin. "Morphological and Immunophenotypic Analysis in Diagnosis of Acute Leukaemia". Delta Medical College Journal 8, n. 1 (31 marzo 2022): 15–20. http://dx.doi.org/10.3329/dmcj.v8i1.58958.

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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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5

Ivanovic, Mirjana, Olivera Jovicic, Jelena Mandic, Dusko Bogetic e Marcello Maddalone. "Oral manifestations of acute leukaemia". Srpski arhiv za celokupno lekarstvo 139, n. 1-2 (2011): 103–6. http://dx.doi.org/10.2298/sarh1102103i.

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Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.
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6

Budi, Luh Putu Rihayani, Ketut Ariawati e Sianny Herawati. "NEONATAL ACUTE MYELOID LEUKAEMIA". INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 19, n. 3 (14 ottobre 2016): 211. http://dx.doi.org/10.24293/ijcpml.v19i3.417.

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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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7

Jeong, E., H. J. Park, J. Y. Lee e B. K. Cho. "Leukaemic macrocheilia in acute myeloblastic leukaemia". British Journal of Dermatology 151, n. 5 (novembre 2004): 1102. http://dx.doi.org/10.1111/j.1365-2133.2004.06242.x.

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8

Dachi. "Acute Leukaemias in Bauchi State, Northeastern Nigeria: Pattern of Presentations and Clinical Entities". West Africa Journal of Medicine 39, n. 5 (26 giugno 2022): 497–500. http://dx.doi.org/10.55891/wajm.v39i5.122.

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Abstract (sommario):
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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9

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, n. 1 (12 aprile 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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Sedick, Qanita, Sultan Alotaibi, Saeed Alshieban, Khalid Ben Naheet e Ghaleb Elyamany. "Natural Killer Cell Lymphoblastic Leukaemia/Lymphoma: Case Report and Review of the Recent Literature". Case Reports in Oncology 10, n. 2 (7 luglio 2017): 588–95. http://dx.doi.org/10.1159/000477843.

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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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Kuek, Vincent, Anastasia M. Hughes, Rishi S. Kotecha e Laurence C. Cheung. "Therapeutic Targeting of the Leukaemia Microenvironment". International Journal of Molecular Sciences 22, n. 13 (26 giugno 2021): 6888. http://dx.doi.org/10.3390/ijms22136888.

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In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia.
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Yook, Hwa Jung, Joon Ho Son, Yeong Ho Kim, Ju Hee Han, Ji Hyun Lee, Young Min Park, Nack-Gyun Chung, Hee Je Kim e Chul Hwan Bang. "Leukaemia Cutis: Clinical Features and Outcomes of 56 Patients". Acta Dermato-Venereologica 102 (11 febbraio 2022): adv00647. http://dx.doi.org/10.2340/actadv.v102.1123.

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Leukaemia is a malignant neoplasm of the haematopoietic system. Cutaneous manifestations of leukaemia are called leukaemia cutis, and are regarded as a sign of poorer prognosis and shorter survival time. A single-institution retrospective review was performed of medical records of patients diagnosed with leukaemia cutis in the dermatology department of Seoul St Mary’s Hospital between January 2012 and April 2021. Fifty-six cases with cutaneous leukaemic involvement and underlying haematological malignancy were included (40 acute myelogenous leukaemia, 8 acute lymphoblastic leukaemia, 3 chronic myeloid leukaemia, 2 chronic lymphocytic leukaemia, and 3 myelodysplastic syndrome). Male-female ratio 1.9:1, mean age at diagnosis 45.8 years. Plaques (28%) and papules (27%) were the most common skin lesions, followed by patches (18%) and nodules (16%). Mean time from diagnosis of leukaemia to development of leukaemia cutis was 12.3 months. Forty-six patients (84%) died during the 7-year follow-up; mean time from diagnosis of leukaemia cutis to death was 5.4 months. The results suggest that leukaemia cutis is associated with poor outcomes in patients with leukaemia. Comprehensive skin examination of these patients may help diagnose leukaemia cutis early, enabling prompt treatment.
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Ou, Ming-Che, Wen-Lee Hwang e Chieh-Lin Teng. "Leukaemic pleural effusion in acute myeloid leukaemia". British Journal of Haematology 154, n. 6 (17 maggio 2011): 669. http://dx.doi.org/10.1111/j.1365-2141.2011.08722.x.

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Okikiolu, Jumoke, Richard Dillon e Kavita Raj. "Acute leukaemia". Medicine 49, n. 5 (maggio 2021): 274–81. http://dx.doi.org/10.1016/j.mpmed.2021.02.004.

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Mehta, Milan M., Timothy S. Kemp e Faddy Hardo. "Acute Leukaemia". InnovAiT: Education and inspiration for general practice 2, n. 8 (20 luglio 2009): 458–65. http://dx.doi.org/10.1093/innovait/inp113.

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Abstract (sommario):
A cute leukaemias are malignant disorders that arise from the clonal proliferation of a single haematopoietic stem cell. The morbidity and mortality associated with acute leukaemias are due to the effects of bone marrow failure which arises from the accumulation of abnormal blood cells in the bone marrow.
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16

Treleaven, Jennie, e Simon T. Meller. "Acute Leukaemia". Medicine 28, n. 3 (2000): 58–64. http://dx.doi.org/10.1383/medc.28.3.58.28367.

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Treleaven, Jennie, e Simon T. Meller. "Acute leukaemia". Medicine 32, n. 6 (giugno 2004): 65–69. http://dx.doi.org/10.1383/medc.32.6.65.36661.

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Raj, Kavita. "Acute leukaemia". Medicine 41, n. 5 (maggio 2013): 269–74. http://dx.doi.org/10.1016/j.mpmed.2013.03.011.

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Mwirigi, Anne, Richard Dillon e Kavita Raj. "Acute leukaemia". Medicine 45, n. 5 (maggio 2017): 280–86. http://dx.doi.org/10.1016/j.mpmed.2017.02.010.

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Foa, Robin, Alessandro Cignetti e Anna Guarini. "Acute Leukaemia". Clinical Immunotherapeutics 6, n. 3 (settembre 1996): 238–49. http://dx.doi.org/10.1007/bf03259522.

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Gurusamy, Veeraraghavan, Ramya Panneerselvam e Bharathi Vidhya Jayanthi. "Mixed phenotype acute leukaemia: a case report of an unusual presentation". International Journal of Research in Medical Sciences 5, n. 7 (24 giugno 2017): 3247. http://dx.doi.org/10.18203/2320-6012.ijrms20173024.

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Mixed phenotype acute leukaemias (MPALs), a varied group of disorders pose a diagnostic challenge to the physicians and pathologists alike. This rare subset of acute leukaemias are characterised by the presence of blasts which express markers of more than one lineage (B-lymphoid / T-lymphoid / Myeloid lineage), making the essentiality of immunophenotyping more pertinent. MPALs are included in the acute leukaemias of ambiguous lineage under the World health organization (WHO) classification of tumours of haematopoietic and lymphoid tissues. We describe here a case report of mixed phenotype acute leukaemia (T-Lymphoid/Myeloid).
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Atwater, Susan K. "ACUTE PROMYELOCYTIC LEUKAEMIA DEVELOPING INTO ACUTE MYELOBLASTIC LEUKAEMIA". British Journal of Haematology 85, n. 2 (ottobre 1993): 433. http://dx.doi.org/10.1111/j.1365-2141.1993.tb03199.x.

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Jubashi, Tohru. "ACUTE PROMYELOCYTIC LEUKAEMIA DEVELOPING INTO ACUTE MYELOBLASTIC LEUKAEMIA". British Journal of Haematology 85, n. 2 (ottobre 1993): 433. http://dx.doi.org/10.1111/j.1365-2141.1993.tb03200.x.

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Colovic, Natasa, Andrija Bogdanovic, Ana Vidovic, Maja Perunicic-Jovanovic e Milica Colovic. "Granulocytic sarcoma of the femur in a patient with acute megakaryoblastic leukaemia". Srpski arhiv za celokupno lekarstvo 139, n. 11-12 (2011): 805–8. http://dx.doi.org/10.2298/sarh1112805c.

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Introduction. Granulocytic sarcoma, chloroma or myeloblastoma are observed in 3% to7% of acute myeloid leukaemia and represents localized tumour composed of collection of immature leukaemic cells. It appears most frequently in patients with M2, M4 and M5 subtypes of acute myeloid leukaemia Case Outline. A 58-year-old female presented with pain and oedema of the right upper limb in November 2009. After two months the patinet had fracture dislocation and numerous osteolytic lesions of the right femur. Immunohistochemistry of tumour biopsy showed megakaryoblastic granulocytic sarcoma which was CD31++, F-XIII++, CD34-, FVIII+++, S100-, aktin-, EMA++, Bcl2++, CD43++, with positive proliferative marker measured with Ki-67 positivity in more of 50% of cells. Aspirate of bone marrow and immunophenotyping with flowcytometry revealed diagnosis of acute megakaryoblastic leukaemia. The course of the disease was rapid and the patient died before commencing chemotherapy, five months after first complaints. Conclusion. Granulocytic sarcoma is extramedullary localization of collection of leukaemia cells which can proceed, to arise concomitantly with leukaemia, or may be the only manifestation of the disease. The diagnosis can be established only with immunohystochemistry.
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Bhalla, Amit. "Clofarabine: a next-generation deoxyadenosine analogue". International Journal of Basic & Clinical Pharmacology 7, n. 5 (23 aprile 2018): 1048. http://dx.doi.org/10.18203/2319-2003.ijbcp20181660.

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Acute lymphoblastic leukaemia (ALL) is the most common of the paediatric leukaemias. It is estimated that the use of modern combination chemotherapy results in long-term remission in nearly 80% of children diagnosed with ALL. Despite therapy advances, approximately 20% of children with ALL, experience leukaemia relapse. Clofarabine (2-chloro-2’-fluoro-2’-deoxy-9-β-D-arabinofuranosyladenine) is a second-generation nucleoside analogue and is structurally related to fludarabine and cladribine which are widely used in the treatment of lymphoproliferative disorders. Clofarabine exhibits greater affinity to deoxycytidine kinase (dCyd kinase) and prolonged retention in leukaemic blasts compared to fludarabine and cladribine. Clofarabine inhibits both DNA polymerases and ribonucleotide reductase (RNR). This results in impaired DNA synthesis through inhibition of DNA elongation as well as depletion of deoxyribonucleotides. Accumulation of clofarabine triphosphate, in the blasts of patients with refractory leukemia has been demonstrated. Prolonged intracellular half-life of 24 hours for clofarabine triphosphate. Clofarabine is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.
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Niazmand, Mohammad Javad, Matthew Speckert e Donna Johnston. "Acute myeloid leukaemia presenting as proptosis in an infant". BMJ Case Reports 14, n. 12 (dicembre 2021): e247506. http://dx.doi.org/10.1136/bcr-2021-247506.

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Abstract (sommario):
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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Stankovic, Tatjana, e Eliot Marston. "Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia". Srpski arhiv za celokupno lekarstvo 136, n. 3-4 (2008): 187–92. http://dx.doi.org/10.2298/sarh0804187s.

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Abstract (sommario):
Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs) in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR) in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.
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28

Yao, Jie, Qing Huang, Xiao-Bing Zhang e Wei-Ling Fu. "Promoter CpG methylation of oestrogen receptors in leukaemia". Bioscience Reports 29, n. 4 (1 maggio 2009): 211–16. http://dx.doi.org/10.1042/bsr20080140.

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Abstract (sommario):
Previous studies have suggested an important role of ERs (oestrogen receptors) in the pathogenesis of leukaemias. However, there is no information so far about the epigenetic characteristics of ERα isoforms and ERβ in leukaemias. In the present study, the mRNA expression and promoter CpG methylation of ERα isoforms (i.e. ERα-A, -B and -C) and ERβ in leukaemia cell lines were evaluated using RT–PCR (reverse transcription–PCR) and MSP (methylation-specific PCR) respectively. The methylation of ERs was further analysed in acute leukaemia patients by MSP and direct DNA sequencing. Although all ERα isoforms and ERβ were methylated in all leukaemia cell lines, except for ERα-C, which was unmethylated in HL-60 and K562 cell lines, only the expression of ERα-A was deficient in all cell lines and its expression could be reactivated by DNA demethylation reagents. With regard to the methylation characteristics in acute leukaemia patients, only ERα-A was inactivated and specifically methylated (95%; 38/40) in almost all patients and unmethylated in all healthy controls, whereas ERα-B, -C and ERβ were methylated in both patients and healthy controls. This result suggested that the methylated status of ERα-A might serve as an epigenetic biomarker of leukaemias. The present study is the first report that demonstrates selective inactivation of ERα isoforms through the promoter CpG methylation pathway in leukaemias.
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29

Arruda, Walter Oleschko, María Belén Montú, Marcelo de Souza R. de Oliveira e Ricardo Ramina. "Acute myeloid leukaemia induced by mitoxantrone: case report". Arquivos de Neuro-Psiquiatria 63, n. 2a (giugno 2005): 327–29. http://dx.doi.org/10.1590/s0004-282x2005000200024.

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Abstract (sommario):
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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30

Gruszka, Alicja, Debora Valli, Cecilia Restelli e Myriam Alcalay. "Adhesion Deregulation in Acute Myeloid Leukaemia". Cells 8, n. 1 (17 gennaio 2019): 66. http://dx.doi.org/10.3390/cells8010066.

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Abstract (sommario):
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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31

Erdemli, Haci Kemal, Bahattin Adam e Nüket Bavbek. "Pyrimidine 5’Nucleotidase I and II Activities in Acute Leukaemias". Acta Medica (Hradec Kralove, Czech Republic) 47, n. 2 (2004): 129–31. http://dx.doi.org/10.14712/18059694.2018.78.

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Abstract (sommario):
Bacground and objective: Pyrimidine 5’nucleotidase I and II activities of peripheral mononuclear cells were studied to evaluate their role in diagnosis, assessment of therapy and follow up of remission in acute leukaemias. Design and methods: Blood samples were obtained from 40 untreated patients with acute lymphoblastic and myeloid leukaemia and 40 healthy controls, before the therapy and after remission. The correlation between the activity of the enzymes and the efficacy of therapy were established. The enzyme activities were measured by High-Performance Liquid Chromatography (HPLC), using the method described by Amici. For statistical analysis, Mann-Whitney U, Kruskal-Wallis and Wilcoxon methods were used. Results: Before the therapy, Pyrimidine 5’nucleotidase I levels in the leukaemic group were found to be significantly elevated when compared to the control group (p<0.001). Also Pyrimidine 5’nucleotidase II levels were significantly elevated before the therapy and during remission (p<0.02 and p<0.001 respectively). The isoenzyme activities were compared in patients who were in remission, who did not respond to therapy and in patients who died during the therapy, but no significant difference was found. Interpretation and conclusions: We concluded that, Pyrimidine 5’nucleotidase I and II activities can be used as markers for diagnosis and follow up of remission in patients with acute leukaemia. But, they can not have predictive value for prognosis.
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32

Essa, Amr, Maryam Gbadamosi-Akindele e Alan Lichtin. "Isolated CNS leukaemic relapse in acute myeloid leukaemia". BMJ Case Reports 12, n. 12 (dicembre 2019): e233499. http://dx.doi.org/10.1136/bcr-2019-233499.

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33

Jackson, Graham H., e Penelope R. A. Taylor. "Acute Myeloid Leukaemia". Drugs & Aging 19, n. 8 (2002): 571–81. http://dx.doi.org/10.2165/00002512-200219080-00003.

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34

Villela, Luis, e Javier Bolaños-Meade. "Acute Myeloid Leukaemia". Drugs 71, n. 12 (agosto 2011): 1537–50. http://dx.doi.org/10.2165/11593060-000000000-00000.

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35

Stevens, R. F. "Acute myeloid leukaemia". British Medical Bulletin 52, n. 4 (1 ottobre 1996): 764–77. http://dx.doi.org/10.1093/oxfordjournals.bmb.a011581.

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36

Gale, Robert Peter, e Isaac Ben Bassat. "HYBRID ACUTE LEUKAEMIA". British Journal of Haematology 65, n. 3 (7 luglio 2008): 261–64. http://dx.doi.org/10.1111/j.1365-2141.1987.00254.x-i1.

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37

Gonzalez, M., J. F. San Miguel, M. C. Cañizo, A. Orfao, E. Ojeda e A. Lopez Borrasca. "HYBRID ACUTE LEUKAEMIA". British Journal of Haematology 67, n. 1 (settembre 1987): 117–18. http://dx.doi.org/10.1111/j.1365-2141.1987.tb02308.x.

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38

Gale, Robert Peter, e Isaac Ben Bassat. "HYBRID ACUTE LEUKAEMIA". British Journal of Haematology 65, n. 3 (marzo 1987): 261–64. http://dx.doi.org/10.1111/j.1365-2141.1987.tb06851.x.

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39

Avvisati, Giuseppe, Jan Wouter Cate e Franco Mandelli. "ACUTE PROMYELOCYTIC LEUKAEMIA". British Journal of Haematology 81, n. 3 (luglio 1992): 315–20. http://dx.doi.org/10.1111/j.1365-2141.1992.tb08233.x.

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40

Hassan, Sandra, e Matthew Smith. "Acute myeloid leukaemia". Hematology 19, n. 8 (21 novembre 2014): 493–94. http://dx.doi.org/10.1179/1024533214z.000000000312.

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41

Creevy, J. "Acute lymphoblastic leukaemia". Journal of Wound Care 6, n. 10 (2 novembre 1997): 456. http://dx.doi.org/10.12968/jowc.1997.6.10.456.

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42

Estey, Elihu, e Hartmut Döhner. "Acute myeloid leukaemia". Lancet 368, n. 9550 (novembre 2006): 1894–907. http://dx.doi.org/10.1016/s0140-6736(06)69780-8.

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43

Focosi, Daniele. "Acute myeloid leukaemia". Lancet 369, n. 9559 (febbraio 2007): 367. http://dx.doi.org/10.1016/s0140-6736(07)60183-4.

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44

Pinto, A., G. B. Zulian e E. Archimbaud. "Acute myelogenous leukaemia". Critical Reviews in Oncology/Hematology 27, n. 2 (febbraio 1998): 161–64. http://dx.doi.org/10.1016/s1040-8428(97)10029-4.

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45

Pui, Ching-Hon, Leslie L. Robison e A. Thomas Look. "Acute lymphoblastic leukaemia". Lancet 371, n. 9617 (marzo 2008): 1030–43. http://dx.doi.org/10.1016/s0140-6736(08)60457-2.

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46

Ettinger, Lawrence J., Alice G. Ettinger, Vassilios I. Avramis e Paul S. Gaynon. "Acute Lymphoblastic Leukaemia". BioDrugs 7, n. 1 (gennaio 1997): 30–39. http://dx.doi.org/10.2165/00063030-199707010-00005.

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47

Inaba, Hiroto, Mel Greaves e Charles G. Mullighan. "Acute lymphoblastic leukaemia". Lancet 381, n. 9881 (giugno 2013): 1943–55. http://dx.doi.org/10.1016/s0140-6736(12)62187-4.

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48

Malard, Florent, e Mohamad Mohty. "Acute lymphoblastic leukaemia". Lancet 395, n. 10230 (aprile 2020): 1146–62. http://dx.doi.org/10.1016/s0140-6736(19)33018-1.

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49

Fielding, A., S. J. Machin, A. H. Goldstone, E. Solomon e A. Gann. "Acute promyelocytic leukaemia". Lancet 344, n. 8937 (dicembre 1994): 1615–18. http://dx.doi.org/10.1016/s0140-6736(94)90410-3.

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50

Lilleyman, J. S. "Acute lymphoblastic leukaemia". European Journal of Cancer 33, n. 1 (gennaio 1997): 85–90. http://dx.doi.org/10.1016/s0959-8049(96)00428-5.

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