Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification

Abstract

and low survival rates. 1,2 Chromosomal abnormalities and gene mutations are important prognostic factors in AML, but also in other types of leukemia, such as chronic lymphocytic leukemia (CLL). 3,4 INTRODUCTION Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous, complex, and dynamic disease, characterized by multiple somatically acquired genetic events, progression over time,

Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

“…Clinical characteristics such as treatment (low dose treatment), patients' outcome, high LDH level, high PLT count, high WBC count, high cytogenetic and ELN risk, high age (>60 years) at diagnosis, and FLT3 ITD mutation were associated with lower OS (p < 0.01), as expected. Part of the mentioned OS associations have been previously reported in the literature [2,41,52,53] and our group also reported part of these clinical associations on smaller cohorts of AML patients [31,32,53].…”

“…We included only subjects who signed the written informed consent form, with complete laboratory and clinical records, in which the genotyping investigation was successfully performed. AML diagnosis was based on clinical examination and laboratory investigation (including complete blood count, blood smear, bone marrow and/or blood microscopic examination, flow cytometry, cytogenetics, fusion gene investigation as reported previously [30], DNA copy number variations analysis as reported previously [31], fragment analysis for FLT3-ITD and NPM1 mutations as reported previously [32][33][34], and target next-generation sequencing as reported previously [34]).…”

Modelling the Effects of MCM7 Variants, Somatic Mutations, and Clinical Features on Acute Myeloid Leukemia Susceptibility and Prognosis

“…The investigated MCM7 SNPs had no significant effect on OS in either univariable Cox regression analysis or multivariable regression analysis. There were significant associations between OS of AML patients and age at diagnosis > 65 years (p < 0.001), WBC count ≥ 10,000 cells/mm 3 (p = 0.025), LDH ≥ 600IU/L (p = 0.003), ECOG performance status grade ≥2 at diagnosis (p < 0.001), ELN highand intermediate-risk (p < 0.001), and presence of FLT3 ITD mutation (p < 0.001), as we previously reported [30,31]. In addition, we observed an association between lower OS and combined FLT3 ITD/D835 (p = 0.027) and FLT3/DNMT3A (p = 0.039) mutations.…”

A rare case of acute myeloid leukemia with ARHGEF12 (LARG, 11q23.3) and MAPRE1 (EB1, 20q11.21) fusion gene in an elderly patient

“…Moreover, we consider LD-RT-PCR analysis as a rapid and low-cost technique that may be performed for the first investigation of leukemia patients. Our AML patient did not present CNAs, but as previously reported, we agree that MLPA represents a useful analysis for the detection of CNAs with clinical significance (8)(9)(10)(19)(20).…”

“…Fragment analysis and GeneMapper software (ThermoFisher Scientific, USA) were used in order to calculate the Variant-Allele Frequency/Allele Ratio for FLT3 ITD and NPM1 mutations. MLPA analysis was used in order to detect CNAs and aneuploidy identification as previously published (8,9) being well known that MLPA represents a useful analysis for AML patients (8,10). For aneuploidy detection, in addition to the probemix (SALSA P-036 Subtelomere mix 1) used in a published protocol (8), we also used SALSA MLPA P070 Subtelomeres Mix 2B, P181 Centromere mix 1 and P182 Centromere mix 2 (MRC Holland, Amsterdam).…”