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Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic / prognostic potential.

ABSTRACT: Investigating the etiological causes of acute myeloid leukemia (AML) at the molecular level should help in identifying targets and strategies that would increase the efficacy of the current management regimens. Some genes may act as molecular diagnostics, of these ASXL1 and PHF6 are involved in regulation of gene expression, and BAX , and ARC, are pro- and anti-apoptotic molecules, respectively. In this study, peripheral blood samples were collected from 54 recently diagnosed AML patients in addition to 20 healthy individuals (the control group). Cellular RNA was extracted from all the samples and were subjected to quantitative analysis of the transcript levels of the four selected markers. Our data showed a significant elevation in the expression levels of PHF6 and ARC in AML patients, when compared to the controls (77.8% and 83.3%, respectively). On the other hand, ASXL1 and BAX exhibited increase, to a lesser extent, in the expression levels of the AML patients (52% and 55.6%, respectively). Our study also showed that the expression levels of ARC and PHF6 exhibited a concomitant increase and this could be correlated with poor prognosis of the cases. Thus, we can suggest these markers as reliable prognostic markers for prediction of AML outcomes.

SUBMITTER: Mousa NO

PROVIDER: S-EPMC7802071 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic / prognostic potential.

Mousa Nahla O NO Gado Marwa M Assem Magda M MM Dawood Kamal M KM Osman Ahmed A

Genetics and molecular biology 20210106 1

Investigating the etiological causes of acute myeloid leukemia (AML) at the molecular level should help in identifying targets and strategies that would increase the efficacy of the current management regimens. Some genes may act as molecular diagnostics, of these ASXL1 and PHF6 are involved in regulation of gene expression, and BAX , and ARC, are pro- and anti-apoptotic molecules, respectively. In this study, peripheral blood samples were collected from 54 recently diagnosed AML patients in add ...[more]

PMID: 33432966

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Project description:BackgroundAcute myeloid leukemia (AML) is a heterogeneous disease with respect to presentation and clinical outcome. The prognostic value of recently identified somatic mutations has not been systematically evaluated in a phase 3 trial of treatment for AML.MethodsWe performed a mutational analysis of 18 genes in 398 patients younger than 60 years of age who had AML and who were randomly assigned to receive induction therapy with high-dose or standard-dose daunorubicin. We validated our prognostic findings in an independent set of 104 patients.ResultsWe identified at least one somatic alteration in 97.3% of the patients. We found that internal tandem duplication in FLT3 (FLT3-ITD), partial tandem duplication in MLL (MLL-PTD), and mutations in ASXL1 and PHF6 were associated with reduced overall survival (P=0.001 for FLT3-ITD, P=0.009 for MLL-PTD, P=0.05 for ASXL1, and P=0.006 for PHF6); CEBPA and IDH2 mutations were associated with improved overall survival (P=0.05 for CEBPA and P=0.01 for IDH2). The favorable effect of NPM1 mutations was restricted to patients with co-occurring NPM1 and IDH1 or IDH2 mutations. We identified genetic predictors of outcome that improved risk stratification among patients with AML, independently of age, white-cell count, induction dose, and post-remission therapy, and validated the significance of these predictors in an independent cohort. High-dose daunorubicin, as compared with standard-dose daunorubicin, improved the rate of survival among patients with DNMT3A or NPM1 mutations or MLL translocations (P=0.001) but not among patients with wild-type DNMT3A, NPM1, and MLL (P=0.67).ConclusionsWe found that DNMT3A and NPM1 mutations and MLL translocations predicted an improved outcome with high-dose induction chemotherapy in patients with AML. These findings suggest that mutational profiling could potentially be used for risk stratification and to inform prognostic and therapeutic decisions regarding patients with AML. (Funded by the National Cancer Institute and others.).

Dataset Information

Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic / prognostic potential.

Publications

Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic / prognostic potential.

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