Effect of NME2 and SAMHD1 genetic polymorphisms involved in Ara-C metabolism on the response to induction chemotherapy in adult acute myeloid leukemia.
Lamiaa Ahmed Fouad, Ghada Mohamed Elsayed, Mosaad M El-Gammal, Eman Omar Rasekh, Sarah Khaled Ibrahim, Eman Ali Ragab, Fatma B Rashidi
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引用次数: 0
Abstract
Background: Cytarabine is a prodrug which is activated to cytarabine triphosphate (Ara-CTP) through a series of phosphorylation steps. For considerable leukemic cell death, high level of Ara-CTP is required. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) and Nucleotide diphosphate kinase-2 (NME2) are genes involved in Ara-CTP metabolism. To best of our knowledge, there are no similar studies focused on the association of different polymorphisms involved Ara-C metabolism on the response to induction chemotherapy among adult AML Egyptian patients. Therefore, the aim of this study was to determine the effect of SAMHD1 rs28372906 and NME2 rs3744660 polymorphisms on AML complete remission rate (CR), overall survival (OS), and disease-free survival (DFS) among adult AML Egyptian patients, after Ara-C based induction therapy.
Methods: This study was a retrospective conducted at the National Cancer Institute, Cairo University, Egypt. The patient group included 136 adult patients with newly diagnosed AML, while the control group included 48 healthy subjects. The clinical history of all studied patients was collected from patient records. Patients and controls were genotyped for NEM2 (rs3744660) and SAMHD1 (rs28372906) by using Taq Man Genotyping assay and Taq Man genotyping master mix (REF: 4,371,353, Applied Biosystems, USA). Real-time PCR assay was performed on Thermo Fisher Quant Studio™ 3. The Statistical Package for Social Science version 21.0 was used to analyze our data.
Results: Regarding the SAMHD1 (rs28372906) polymorphism, we did not find any genotype variations between patient, and control groups, where all of them were AA genotype. Regarding NME2 (rs3744660) polymorphism the statistical analysis reported significant association between D28 blasts and OS (P-value = 0.043), while the remaining initial patient characteristics and response to induction were not associated with OS.
Conclusion: CR, DFS, and OS were not significantly associated to SAMHD1 rs28372906 and NME2 rs3744660 polymorphisms.
期刊介绍：
As the official publication of the National Cancer Institute, Cairo University, the Journal of the Egyptian National Cancer Institute (JENCI) is an open access peer-reviewed journal that publishes on the latest innovations in oncology and thereby, providing academics and clinicians a leading research platform. JENCI welcomes submissions pertaining to all fields of basic, applied and clinical cancer research. Main topics of interest include: local and systemic anticancer therapy (with specific interest on applied cancer research from developing countries); experimental oncology; early cancer detection; randomized trials (including negatives ones); and key emerging fields of personalized medicine, such as molecular pathology, bioinformatics, and biotechnologies.
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