Effect of NME2 and SAMHD1 genetic polymorphisms involved in Ara-C metabolism on the response to induction chemotherapy in adult acute myeloid leukemia

• Published in: Journal of Egyptian National Cancer Institute Vol. 37; no. 1; pp. 14 - 10
• Main Authors: Fouad, Lamiaa Ahmed, Elsayed, Ghada Mohamed, El-Gammal, Mosaad M., Rasekh, Eman Omar, Ibrahim, Sarah Khaled, Ragab, Eman Ali, Rashidi, Fatma B.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 28.04.2025; Springer; Springer Nature B.V; SpringerOpen
• Subjects: Acute myeloid leukemia; Adolescent; Adult; Aged; Analysis; Aspartate; Blood diseases; Bone marrow; Cancer; Cell death; Chemotherapy; Cytarabine; Cytarabine - administration & dosage; Cytarabine - metabolism; Cytarabine - therapeutic use; Egypt; Ethylenediaminetetraacetic acid; Female; Genetic aspects; Genetic polymorphisms; Genotype; Humans; Induction Chemotherapy - methods; Induction therapy; Kinases; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - pathology; Male; Medical records; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolism; Middle Aged; Mutation; NM23 Nucleoside Diphosphate Kinases - genetics; NME2; Oncology; Patients; Phosphorylation; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Remission (Medicine); Retrospective Studies; SAM Domain and HD Domain-Containing Protein 1 - genetics; SAMHD1; Young Adult; Egypt; United States; United States > US; Acute myeloid leukemia; Cytarabine; Polymorphism; NME2; SAMHD1
• ISSN: 1110-0362; 2589-0409
• DOI: 10.1186/s43046-025-00272-4

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.