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.
Highlights
Acute myeloid leukemia (AML) is characterized by a phenotypic and genetic heterogeneity
We showed that hazard of death for patients with Fms like tyrosine kinase 3 (FLT3) gene mutation and lactate dehydrogenase (LDH) level ≥ 600 IU/L was about two times higher than in patients without FLT3 gene mutation with LDH level < 600 IU/L (HR = 1.80, 95% confidence interval (CI): 1.22–2.66), while an increased hazard of death was observed for patients with LDH level ≥ 600 IU/L within FLT3 strata
Our study indicates that variant genotypes of investigated maintenance complex component 7 (MCM7) single nucleotide polymorphisms (SNPs) are not associated with the risk of AML, clinical features of AML patients, prognosis, or with FLT3, Nucleophosmin 1 (NPM1), and DNA methyltransferase 3 alpha (DNMT3A) mutations
Summary
Acute myeloid leukemia (AML) is characterized by a phenotypic and genetic heterogeneity. Somatic mutations, and epigenetic aberrations have been described to be implicated in the AML susceptibility, pathogenesis, prognosis, evolution, overall survival (OS), or in the treatment response of AML patients [1,2,3,4,5]. The available biomarkers may explain the poor prognosis for just a part of all AML cases; it was supposed that other new markers might be involved [15], such as minichromosome maintenance complex component 7 (MCM7) gene variants, as they have been reported to be associated with relapse in pediatric and adult AML patients and their overall poor survival rate [9,15,16]
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