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

Abstract

The main objective of the study was to evaluate the associations between MCM7 rs2070215, rs1527423, and rs1534309 single nucleotide polymorphisms (SNPs) and acute myeloid leukemia (AML) risk and prognosis. The secondary objectives were to assess if any relationships existed between the mentioned SNPs and FLT3, DNMT3A, NPM1 mutations with clinical outcomes and overall survival (OS) in AML patients. We investigated 281 AML cases and 405 healthy subjects. The results showed a significant association between a variant allele of rs2070215 (p = 0.007), CAT haplotype (p = 0.012), and AML susceptibility. No significant association was found between MCM7 variant genotypes and overall survival of AML patients (p > 0.05), while several associations between somatic mutations, clinical and biological features, and poor OS were noticed. Lactate dehydrogenase (LDH) level ≥ 600 IU/L had a significant effect on the hazard of death (p = 0.004, HR = 1.49, 95% CI: 1.13–1.95). Our study showed that the variant allele of rs2070215, in the allelic model, and CAT haplotype were associated with AML susceptibility. The investigated FLT3, DNMT3A, and NPM1 mutations were associated with the clinical and biological features and poor OS. LDH level ≥ 600 IU/L was associated with an increased hazard of death and this association remained significant when quantifying for effect modification by FLT3 mutation status.

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]).…”

Association between serum lactate dehydrogenase and 60‐day mortality in Chinese Hakka patients with acute myeloid leukemia: A cohort study

“…Interestingly, the statistical results in our study were robust, both nonadjusted and adjusted models; these results are similar to previous studies that LDH is a prognostic factor for AML. 4,16 In particular, the effect was more obvious in those with LDH ≥570 U/L, and such a result may remind the clinicians of devoting more attention and more care to these AML patients.…”

“…Former studies show high concentration of LDH, and age is associated with a high risk for early mortality in AML patients. 10 , 15 , 16 Increased LDH levels are the product of the enhanced glycolytic activity of the tumor and tumor necrosis due to hypoxia, the latter being related to a high tumor burden. 10 Most previous studies have indicated that serum LDH is an independent prognostic factor for patients with AML (non‐APL); 3 , 4 , 17 the higher the serum LDH level, the shorter the survival time.…”

Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

“…Genomic DNA (gDNA) was extracted from peripheral blood specimens collected in 2 mL EDTA vacutainer tubes by using PureLink Genomic DNA Mini Kits (Thermo Fisher Scientific, Waltham, MA, USA) and Wizard Genomic DNA Purification kits (Promega, Madison, WI, USA) with minor modification [ 25 ]. The concentration and purity of the obtained DNA samples were measured by a BioSpectrometer basic (Eppendorf, Wien, Austria).…”