Academic literature on the topic 'Acute Lymphoblastic Leukemia, children, IKAROS, miRNA'
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Journal articles on the topic "Acute Lymphoblastic Leukemia, children, IKAROS, miRNA"
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Vasquez, Marina Lipkin, Stefano Volinia, Cecilia Fernandez, Nicola Zanesi, Grazia Fazio, Ilana Renault Zalcberg, Ramiro Garzon, Giovanni Cazzaniga, Andrea Biondi, and Carlo M. Croce. "Multivariate Analysis Reveals a miRNA Profile Correlated To Karyotype and Outcome In Pediatric B-Cell Precursor ALL." Blood 122, no. 21 (November 15, 2013): 2597. http://dx.doi.org/10.1182/blood.v122.21.2597.2597.
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Abstract Acute lymphoblastic leukemia (ALL) is the commonest childhood cancer and is characterized by the presence of recurring structural genetic alterations that have been associated to clinical response.Recently it has been shown that the deregulation of microRNAs (miRNA), a class of small RNAs that negatively control gene expression, is a common characteristic of hematological malignancies and may be related to the pathogenesis of leukemias. The aim of the current study was to explore which microRNAs are expressed by each subtype of pediatric B-cell precursor ALL and to determine their roles into clinical outcome. We analyzed samples from 94 children diagnosed as B-cell precursor ALL in Italy between 2000 and 2010 that were included in the AIEOP-BFM protocol of treatment. The patients were divided by cytogenetic subgroups of ALL. Cells CD34+ and CD19+ from healthy donors were used as negative controls. The miRNA signature was studied using microchips for miRNA microarray. We first performed a two-class comparison of miRNA expression between leukemic and non-leukemic samples and found 84 miRNAs differently expressed (P<0.01). A multivariate analysis of karyotype showed that 59 of these miRNAs were correlated to leukemia (P<0.01). All major subtypes of precursor B-cell ALL were analyzed: MLL-rearranged (10), TEL-AML1(15), E2A-PBX1(10), BCR-ABL(23), hyperdiploid(17), ‘normal Karyotype’ (19, defined as those not carrying the foregoing cytogenetic aberrations), and also the presence of IKAROS deletions was evaluated. Each subgroup was found to have unique microRNA-signature that differed from each other and from those of healthy hematopoietic cells. Both Kaplan Meier and Cox regression tests were performed to check how many of these miRNAs were correlated to clinic response, based on the induction failure, relapse, and survival. A multivariate analysis revealed that genetic subtypes and poor-responders patients display characteristic miRNA signatures. Specifically the mir-125b, 16-2, 24, 28-5p, 128a, 138-1 and 658 (all P<0.01) came out as independent prognostic factors predictive of event-free survival (EFS). IKAROS deletions did not come out as an independent prognostic factor, probably for being already associated to Ph+ and “BCR-ABL like” patients, who already have a poor prognosis. In addition, our group has previously shown that miR-125b may act as an oncogene and is correlated to a poor response in Ph+ samples, also increasing therapy resistance and leukemia aggressiveness in vivo. Further functional studies are needed to better explain the role of these miRNA and to provide new insights into the biology of pediatric ALL. Disclosures: Garzon: Karyopharm : Research Funding.
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Vasquez, Marina Lipkin, Nicola Zanesi, Stefano Volinia, Ramiro Garzon, Giovanni Cazzaniga, Carlo M. Croce, and Andrea Biondi. "MiR-125b Cooperates with BCR-ABL and Enhances Therapy Resistance in Childhood Ph+ ALL." Blood 118, no. 21 (November 18, 2011): 78. http://dx.doi.org/10.1182/blood.v118.21.78.78.
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Abstract Abstract 78 The treatment improvements in the past two decades led childhood acute lymphoblastic leukemia (ALL) cure rates reach over 80%, but children who carry the Philadelphia (Ph+) chromosome still have high risk of relapse due to therapy resistance. Different results with large series of patients have shown that an earlier remission after induction with glucocorticoids and intrathecal methotrexate is correlated to a better outcome. Besides, the minimal residual disease (MRD) risk measured after induction is also correlated to the therapy response, indicating that an early response can predict Ph+ ALL overall outcome. Several studies have shown that Ph+ ALL is heterogeneous in terms of clinical parameters even if all patients carry BCR-ABL and most of them carry the oncogenic isoform of IKAROS. They respond differently to the treatment, which suggests the presence of additional mechanisms involved in leukemogenesis. In an attempt to find secondary genetic abnormalities that may be responsible for the Ph+ ALL chemo resistance and heterogeneity, we studied the miRNA expression profile in two patient groups discriminated by the initial therapy response. We included samples from 78 consecutive Ph+ ALL children diagnosed in Italy between 2000 and 2010. The miRNA signature was analyzed by miRNA array using Applied Biosystems Array-Cards comparing two patient groups differentiated according to MRD and prednisone response. A particular miRNA profile was found in the poor responder group and it was confirmed using specific miRNA single assays from AB. Specially the miR-125b was up to ten-fold overexpressed compared to the good responder group (p =.006). To investigate the functional role of miR-125b in Ph+ ALL we used BCR-ABL positive cell lines (3 ALL and one CML in blast-crisis) to create a xenograft leukemia model and induced miRNA upregulation by direct inoculation of synthetic miR-125b (premiR). Tumors injected with premiR-125b (n=14) were significantly bigger than the scrambled oligonucleotide (n=10) and mock controls (n=4) (p=.04). After two weeks the premiR-125b tumors grew six-fold more than controls and average tumor weights for the scrambled oligonucleotides and the premiR-125b inoculated mice were 0.63 g and 1.56 g, respectively (p =.01). Further, we determined whether miR-125b protects the tumor cells from apoptosis after treatment with Dexamethasone. While tumors injected with scrambled molecules were 70% reduced after 10 days of corticoid treatment, tumors injected with premiR-125b were only 30% reduced (p=.05). Together, these results suggest that miR-125b acts as an oncogene in Ph+ ALL and its overexpression accelerates the role of BCR-ABL, increasing therapy resistance and leukemia aggressiveness. Additional studies will be necessary to understand why this miRNA is overexpressed in some patients and how it acts in cooperation with BCR-ABL to induce leukemia. In the future, novel therapies using miRNAs as targets can emerge as strategies to be added to the anti-tyrosine kinase drugs in order to improve treatment response and survivor in Ph+ ALL. Disclosures: No relevant conflicts of interest to declare.
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Kogut, Sophie, Hana Paculova, Princess Rodriguez, Joseph Boyd, Alyssa Richman, Amrita Palaria, Hilde Schjerven, and Seth Frietze. "Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia." Epigenomes 6, no. 4 (October 19, 2022): 37. http://dx.doi.org/10.3390/epigenomes6040037.
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The hematopoietic transcription factor Ikaros (IKZF1) regulates normal B cell development and functions as a tumor suppressor in precursor B cell acute lymphoblastic leukemia (B-ALL). MicroRNAs (miRNAs) are small regulatory RNAs that through post-transcriptional gene regulation play critical roles in intracellular processes including cell growth in cancer. However, the role of Ikaros in the regulation of miRNA expression in developing B cells is unknown. In this study, we examined the Ikaros-regulated miRNA targets using human IKZF1-mutated Ph+ B-ALL cell lines. Inducible expression of wild-type Ikaros (the Ik1 isoform) caused B-ALL growth arrest and exit from the cell cycle. Global miRNA expression analysis revealed a total of 31 miRNAs regulated by IK1, and ChIP-seq analysis showed that Ikaros bound to several Ik1-responsive miRNA genes. Examination of the prognostic significance of miRNA expression in B-ALL indicate that the IK1-regulated miRNAs hsa-miR-26b, hsa-miR-130b and hsa-miR-4649 are significantly associated with outcome in B-ALL. Our findings establish a potential regulatory circuit between the tumor-suppressor Ikaros and the oncogenic miRNA networks in IKZF1-mutated B-ALL. These results indicate that Ikaros regulates the expression of a subset of miRNAs, of which several may contribute to B-ALL growth.
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Sun, Lei, Patricia A. Goodman, Carla M. Wood, Mya-Lisa Crotty, Martha Sensel, Harland Sather, Christopher Navara, et al. "Expression of Aberrantly Spliced Oncogenic Ikaros Isoforms in Childhood Acute Lymphoblastic Leukemia." Journal of Clinical Oncology 17, no. 12 (December 1999): 3753–66. http://dx.doi.org/10.1200/jco.1999.17.12.3753.
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PURPOSE: We sought to determine if molecular abnormalities involving the Ikaros gene could contribute to the development of acute lymphoblastic leukemia (ALL) in children. PATIENTS AND METHODS: We studied Ikaros gene expression in normal human bone marrow, normal thymocytes, normal fetal liver–derived immature lymphocyte precursor cell lines, eight different ALL cell lines, and leukemic cells from 69 children with ALL (T-lineage ALL, n = 18; B-lineage ALL, n = 51). Expression of Ikaros protein and its subcellular localization were examined by immunoblotting and confocal laser-scanning microscopy, respectively. Polymerase chain reaction (PCR) and nucleotide sequencing were used to identify the specific Ikaros isoforms expressed in these cells. Genomic sequencing of splice junction regions of the Ikaros gene was performed in search for mutations. RESULTS: In each of the ALL cases, we found high-level expression of a non–DNA-binding or aberrant DNA-binding isoform of Ikaros with abnormal subcellular compartmentalization patterns. In contrast, only wild-type Ik-1 and Ik-2 isoforms with normal subcellular localization were found in normal bone marrow cells and thymus-derived or fetal liver–derived normal lymphocyte precursors. In leukemic cells expressing the aberrant Ikaros coding sequences with the 30-base-pair deletion, genomic sequence analysis of the intron-exon junctions between exons 6 and 7 yielded the wild-type sequence. We identified a single nucleotide polymorphism (SNP) affecting the third base of the triplet codon for a proline (CCC or CCA) in the highly conserved bipartite activation region (viz, A or C at position 1002 numbering from the translation start site of Ik-1) within our Ikaros clones. Bi-allelic expression of truncated and/or non–DNA-binding isoforms along with wild-type isoforms was observed in leukemic cells, which implicates trans-acting factor(s) affecting splice site recognition. CONCLUSION: Our findings link specific molecular defects involving the Ikaros gene to childhood ALL. Posttranscriptional regulation of alternative splicing of Ikaros RNA seems to be defective in leukemic lymphocyte precursors from most children with ALL. Consequently, leukemic cells from ALL patients, in contrast to normal lymphocyte precursors, express high levels of non–DNA-binding Ikaros isoforms that are reminiscent of the non–DNA-binding Ikaros isoforms that lead to lymphoblastic leukemia in mice.
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Yang, Yung-Li, Sung-Liang Yu, Hsuan-Yu Chen, Pan-Chyr Yang, Jiann-Shiuh Chen, Dong-Tsamn Lin, Shu-Rung Lin, et al. "MicroRNA Expression in Childhood Acute Lymphoblastic Leukemia (ALL)." Blood 112, no. 11 (November 16, 2008): 4467. http://dx.doi.org/10.1182/blood.v112.11.4467.4467.
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Abstract MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are regulators of gene expression. A role for microRNAs in leukemia, such as chronic lymphoblastic leukemia, acute myelogeneous leukemia has recently been recognized. However, little is known about the role of microRNAs in childhood acute lymphoblastic leukemia (ALL). To determine whether miRNAs are associated with the clinical features of childhood ALL and its association with cytogenetic abnormalities, we analyzed 60 untreated childhood ALL cases for their miRNA expression using a microarray platform. Leukemic samples were collected from the ALL children between 1–18 years of age. Of the 365 miRNA analyzed with a training group of 40 patients, a miRNA signature was derived that was associated with event-free survival. The signature was tested in a validation group of 20 patients. For the latter, a miRNA compound covariate predictor (i.e., a miRNA risk score) was computed on the basis of weighted levels of the miRNAs forming the outcome signature. The signature identified from the training group contained 5 miRNA highly associated with event-free survival (P<0.05). The summary value of the signature miRNA was also highly associated with event-free survival (P <0.05) in the validation group. After adjustment for the gender, age, initial white counts, immunophenotypes, and cytogenetics, the miRNA risk score remained associated with event-free survival (P <0.05) in multivariable analysis. In conclusion, we have identified a miRNA signature of 5 miRNAs which is highly associated with the clinical outcome, cytogenetic and immunophenotypic subtypes of childhood ALL.
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Ge, Zheng, Chunhua Song, Yali Ding, Bi-Hua Tan, Dhimant Desai, Arati Sharma, Raghavendra Gowda, et al. "Dual targeting of MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia." Leukemia 35, no. 5 (February 2, 2021): 1267–78. http://dx.doi.org/10.1038/s41375-021-01132-5.
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AbstractChildren of Hispanic/Latino ancestry have increased incidence of high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) with poor prognosis. This leukemia is characterized by a single-copy deletion of the IKZF1 (IKAROS) tumor suppressor and increased activation of the PI3K/AKT/mTOR pathway. This identifies mTOR as an attractive therapeutic target in HR B-ALL. Here, we report that IKAROS represses MTOR transcription and IKAROS’ ability to repress MTOR in leukemia is impaired by oncogenic CK2 kinase. Treatment with the CK2 inhibitor, CX-4945, enhances IKAROS activity as a repressor of MTOR, resulting in reduced expression of MTOR in HR B-ALL. Thus, we designed a novel therapeutic approach that implements dual targeting of mTOR: direct inhibition of the mTOR protein (with rapamycin), in combination with IKAROS-mediated transcriptional repression of the MTOR gene (using the CK2 inhibitor, CX-4945). Combination treatment with rapamycin and CX-4945 shows synergistic therapeutic effects in vitro and in patient-derived xenografts from Hispanic/Latino children with HR B-ALL. These data suggest that such therapy has the potential to reduce the health disparity in HR B-ALL among Hispanic/Latino children. The dual targeting of oncogene transcription, combined with inhibition of the corresponding oncoprotein provides a paradigm for a novel precision medicine approach for treating hematological malignancies.
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Zhou, Fen, Heng Mei, Runming Jin, Xiaoqing Li, and Xiangjun Chen. "Expression of Ikaros Isoform 6 in Chinese Children With Acute Lymphoblastic Leukemia." Journal of Pediatric Hematology/Oncology 33, no. 6 (August 2011): 429–32. http://dx.doi.org/10.1097/mph.0b013e318217f5f2.
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Dovat, Sinisa, Yali Ding, Dhimant Desai, and Arati Sharma. "Abstract A088: Targeting endoplasmic reticulum stress-induced apoptosis to reduce health disparity in high-risk B-cell acute lymphoblastic leukemia in Hispanic/Latino children." Cancer Epidemiology, Biomarkers & Prevention 32, no. 1_Supplement (January 1, 2023): A088. http://dx.doi.org/10.1158/1538-7755.disp22-a088.
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Abstract B-cell Acute Lymphoblastic Leukemia (ALL) is the most common childhood malignancy. The death rate from B-ALL in Hispanic/Latino (H/L) is 40% higher than in non-Hispanic whites (NHW) after correcting socioeconomic factors. Deletion of one IKZF1 allele is highly increased H/L children, which provides a biological rationale for the worse prognosis of B-ALL in this population. The very high incidence (31% in all children and 65% in children ≥10 yrs) makes the deletion of one IKZF1 allele the most frequent genetic alteration that confers adverse prognosis in B-ALL in H/L children. The IKZF1 gene encodes a DNA-binding protein, IKAROS, which functions as a transcriptional regulator. Identification of IKAROS target genes in B-ALL of H/L children is essential to understand the specificity of B-ALL pathogenesis in those children and develop the targeted treatment to reduce the health disparity in survival for H/L children with B-ALL. Global DNA-binding analysis of primary B-ALL cells from H/L children showed that IKAROS binds to the promoter of eukaryotic elongation factor 2 kinase (eEF2K). eEF2K regulates protein synthesis, cell cycle progression and malignant transformation. The activity of eEF2K is increased in human malignancies, including B-ALL, and eEF2K is a critical regulator of endoplasmic reticulum (ER) stress-induced autophagy and apoptosis in tumor cells. The role of IKAROS in the regulation of eEF2K expression in B-ALL of H/L children was established using gain-of-function and loss-of-function experiments. Overexpression of IKZF1 in H/L B-ALL cells results in reduced expression of eEF2K, while IKZF1 knock-down results in increased transcription of eEF2K in H/L B-ALL. Since IKAROS function in leukemia is regulated by pro-oncogenic Casein Kinase 2 (CK2), we tested whether CK2 can control the ability of IKAROS to regulate the expression of eEF2K in H/L B-ALL. Increased expression of CK2 in H/L B-ALL results in increased expression of the eEF2K gene due to the loss of IKAROS binding to the promoter of the eEF2K genes. Inhibition of CK2 with shRNA and/or a specific CK2 inhibitor, CX-4945, restores IKAROS binding to promoter of eEF2K in high-risk B-ALL with deletion of one IKZF1 allele in H/L children. Restoration of IKAROS binding to promoter of eEF2K in high-risk B-ALL in H/L children results in reduced expression of this gene. This was associated with increased sensitivity to Akt inhibition by MK-2206. Combination treatment with CK2 inhibitor and MK-2206 showed a synergistic effect on B-ALL cells from H/L children. In summary, presented data demonstrate that IKAROS and CK2 regulate ER stress-induced apoptosis via regulation of eEF2K expression in high-risk B-ALL in Hispanic/Latino children. Results suggest that targeting ER stress-induced apoptosis in combination with CK2 inhibitors can be an efficient treatment to reduce the health disparity in survival for Hispanic/Latino children with B-ALL. Citation Format: Sinisa Dovat, Yali Ding, Dhimant Desai, Arati Sharma. Targeting endoplasmic reticulum stress-induced apoptosis to reduce health disparity in high-risk B-cell acute lymphoblastic leukemia in Hispanic/Latino children [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A088.
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Gutierrez-Camino, Angela, Susana Garcia-Obregon, Elixabet Lopez-Lopez, Itziar Astigarraga, and Africa Garcia-Orad. "miRNA deregulation in childhood acute lymphoblastic leukemia: a systematic review." Epigenomics 12, no. 1 (January 2020): 69–80. http://dx.doi.org/10.2217/epi-2019-0154.
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Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent causes of death by disease in children. Accurate patient risk stratification based on genetic markers could increases survival rates. miRNAs can represent novel candidates with diagnostic, predictive and prognostic potential; however, many groups investigated their involvement with contradictory results. Aim: To clarify the role of miRNAs as biomarkers through a systematic review. Results: From a revision of 45 manuscripts, we found that miR-128 and miR-181 overexpression could represent markers for ALL diagnosis and underexpression of miR-708 and miR-99a could be markers for bad prognosis. Conclusion: These signatures could refine classification and risk stratification of patients and improve ALL outcome.
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Veer, Arian Van Der, Marieke E. Willemse, Valerie De Haas, Anjo J. P. Veerman, Willem A. Kamps, Rob Pieters, and Monique L. Den Boer. "Unfavorable Prognostic Value of IKAROS but Not CRLF2 in Children with BCRABL1-positive Acute Lymphoblastic Leukemia,." Blood 118, no. 21 (November 18, 2011): 3528. http://dx.doi.org/10.1182/blood.v118.21.3528.3528.
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Abstract Abstract 3528 Despite the relative high success-rate to treat children (<18 yrs) with precursor B-ALL (5-year event-free survival >80%), the prognosis of the subtype of BCRABL1- positive ALL remains poor (5-year event-free survival <50%). Patients carrying this translocation are treated according to intensified high-risk protocols which are, however, associated with therapy-related side-effects and mortality. A different treatment for those cases at high risk of treatment failure and less treatment for those at low risk of treatment failure is preferred to improve overall outcome results in children with BCRABL1 -positive ALL. Deletions in the gene encoding Ikaros (IKZF1) and an aberrant high expression level of the cytokine receptor-like factor 2 gene (CRLF2) have both recently been associated with a poor prognosis of children with newly diagnosed precursor B-ALL. We here studied whether these genomic abnormalities can also serve as prognostic factor within the subset of BCRABL1 -positive pediatric ALL. Methods; Leukemic cells of BCRABL1- positive patients enrolled in two consecutive treatment protocols of the Dutch Childhood Oncology Group (DCOG) were analyzed for IKZF1 and CRLF2 status. IKZF1 deletions were determined by Multiplex Ligation Probe-based Amplification assays (MLPA) and comparative genomic hybridization arrays (aCGH; Agilent, Sureprint G3 Human CG 180K). The p335 MPLA assay (MRC Holland) was used for discovery of IKZF1 deletions and data were validated by aCGH and a second MLPA assay (p202; MRC Holland) with higher resolution for affected regions. CRLF2 expression levels were determined by Affymetrix U133 plus 2.0 gene expression arrays. A large cohort of 459 newly diagnosed ALL cases served as reference. A high level of CRLF2 expression was assigned to 10% of all cases ranked according to CRLF2 expression level. Results; Deletions in IKZF1 were found in 65% of the cases (n=11); 10 cases had a partial deletion between exon 2 and 7 of IKZF1 resulting in a dominant negative variant and 1 case had a deletion of the complete IKZF1 gene. Analysis of patient characteristics revealed that cases with deletions in IKZF1 have a median 4.5-fold higher white blood cell count compared to unaffected cases (p=0.009). Analysis of the cumulative incidence of relapse (pCIR) with death as a competing risk indicated that children with IKZF1 -deleted BCRABL1 -positive ALL had a significantly increased risk of developing a relapse compared with those with an unaffected IKZF1 gene (73% versus 17%, p=0.02). As a consequence, the 5-year event-free survival was also lower for the IKZF1- deleted group compared to the unaffected group (18% versus 67% p=0.04, Log-Rank). The expression level of CRLF2 in BCRABL1- positive cases was median 91.4 arbitrary units (p25-p75: 84.2–97.2) compared to 91.3 arbitrary units (p25-p75: 82.6–107.3) for BCRABL1 -negative cases (p>0.05). Expression of none of the BCRABL1 -positive ALL cases was ranked within the highest 10% percentile of the reference group. Hence, high expression of CRLF2 cannot explain a poor prognosis of BCRABL1- positive cases. In conclusion, our data show that a deletion of IKZF1 but not a high expression of CRLF2 is a strong discriminative prognostic factor in BCRABL1- positive pediatric precursor B-ALL. We therefore advocate to implement the IKZF1 status as a new prognostic factor in BCRABL1- positive pediatric ALL. Disclosures: No relevant conflicts of interest to declare.
Dissertations / Theses on the topic "Acute Lymphoblastic Leukemia, children, IKAROS, miRNA"
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LIPKIN, VASQUEZ MARINA. "Unveiling the heterogeneity within chilhood Ph+ acute lymphoblastic leukemia." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/20633.
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In the past two decades, childhood acute lymphoblastic leukemia (ALL) cure rate has reached over 80% due to treatment advances, but some resistant ALL subtypes, such as those that carry the Philadelphia (Ph+) chromosome, still don’t respond to therapy. The presence of BCR-ABL in ALL children is correlated to a very poor prognosis, nevertheless, several long-scale studies have shown that Ph+ ALL is heterogeneous in terms of clinical parameters and patients respond differently to the therapy, what suggests the presence of additional mechanisms of leukemogenesis. A set of international studies with large series of patients have shown that an earlier remission after induction with glucocorticoids and intrathecal methotrexate (IT MTX) is correlated to a better outcome. In the present study we looked for secondary genetic lesions in a group of 78 consecutive Ph+ ALL children diagnosed in Italy between 2000 and 2010, specifically studying deletions in the IKZF1 gene and the miRNA profile according to the first therapy response. The IKZF1 gene was studied by PCR, direct sequencing and SNP array and a high incidence of deletions (70%) was detected in our children, specially the d4-7(62%). The miRNA signature was analysed by miRNA array comparing two groups of patients differentiated according to MRD/prednisone response. Particularly miR-221, 222 and miR-125b-2 are highly overexpressed in the poor responder group of patients. We showed in vivo that miR-125b-2 acts as oncogene and increases leukemia aggressiveness. Further studies will be necessary to understand how IKZF1, miR-221,222 and 125b act in cooperation with BCR-ABL to induce leukemia. In the future, novel target therapies can emerge as pro-apoptotic approaches to be added to the anti-tyrosine kinase drugs in order to improve response and survivor in Ph+ ALL.
Book chapters on the topic "Acute Lymphoblastic Leukemia, children, IKAROS, miRNA"
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Becerra Becerra, Edgardo, and Guadalupe García-Alcocer. "MicroRNAs and Their Role in Acute Lymphoblastic Leukemia." In Acute Leukemias [Working Title]. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.94960.
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Acute lymphoblastic leukemia (ALL) has been established as the most common acute leukemia in children, accounting for 80–85% of cases. ALL occurs mostly in children and it is considered as a high-risk disease in the elderlies. ALL is characterized by a clonal disorder where the normal hematopoiesis is replaced by a malignant clonal expansion of lymphoid progenitors. Although many therapeutic strategies have been established to treat ALL leading to improved survival rates, the short-term and long-term complications derived from treatment toxicity represent a critical risk for patients. The treatment-related toxicity suggests a need for the development of new therapy strategies to effectively treat high-risk and low-risk disease. Nowadays, an important approach is focused on the identification of molecules involved in the mechanisms that lead to leukemia generation and progression to determine potential targets at the transcriptional level. MicroRNAs (miRNAs) are a group of key molecules that regulate signaling pathways related to lymphopoiesis. miRNAs participate in the regulation of hematopoietic differentiation and proliferation, as well as their activity. The present review details the recompilation of evidences about the relation between miRNAs and lymphopoiesis, ALL development and progression in order to propose and explore novel strategies to modulate ALL-related miRNA levels as a therapeutic approach.
Conference papers on the topic "Acute Lymphoblastic Leukemia, children, IKAROS, miRNA"
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Dovat, Sinisa, Zheng Ge, Chunhua Song, and Kimberly J. Payne. "Abstract B45: Regulation of CRLF2 oncogene expression by the Ikaros tumor suppressor in B cell acute lymphoblastic leukemia that occurs at high frequency in Hispanic children." In Abstracts: Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; September 25-28, 2016; Fort Lauderdale, FL. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7755.disp16-b45.
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