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Open AccessArticle

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

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Genetics Department, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Mureș, Romania
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Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research of the “George Emil Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Mureș, Romania
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Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy “Iuliu Haţieganu” from Cluj Napoca, 400000 Cluj-Napoca, Romania
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Department of Medical Genetics, University of Medicine and Pharmacy “Iuliu Haţieganu” from Cluj-Napoca, 400000 Cluj-Napoca, Romania
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Department of Hematology, “Ion Chiricuta” Clinical Cancer Center, 400015 Cluj-Napoca, Romania
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Department of Internal Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureş, 540139 Mureș, Romania
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Authors to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 158; https://doi.org/10.3390/jcm9010158
Received: 27 November 2019 / Revised: 21 December 2019 / Accepted: 6 January 2020 / Published: 8 January 2020
(This article belongs to the Section Hematology)
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. View Full-Text
Keywords: MCM7; acute myeloid leukemia; FLT3; NPM1; DNMT3A; WBC; LDH MCM7; acute myeloid leukemia; FLT3; NPM1; DNMT3A; WBC; LDH
MDPI and ACS Style

Tripon, F.; Iancu, M.; Trifa, A.; Crauciuc, G.A.; Boglis, A.; Dima, D.; Lazar, E.; Bănescu, C. Modelling the Effects of MCM7 Variants, Somatic Mutations, and Clinical Features on Acute Myeloid Leukemia Susceptibility and Prognosis. J. Clin. Med. 2020, 9, 158.

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