参与阿糖胞苷代谢的NME2和SAMHD1基因多态性对成人急性髓系白血病诱导化疗反应的影响。

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

作者信息

Fouad Lamiaa Ahmed, Elsayed Ghada Mohamed, El-Gammal Mosaad M, Rasekh Eman Omar, Ibrahim Sarah Khaled, Ragab Eman Ali, Rashidi Fatma B

机构信息

Chemistry Department, Faculty of Science, Biochemistry Division, Cairo University, Cairo, Egypt.

Clinical Pathology Department, National Cancer Institute-Cairo University, Cairo, Egypt.

出版信息

J Egypt Natl Canc Inst. 2025 Apr 28;37(1):14. doi: 10.1186/s43046-025-00272-4.

DOI:10.1186/s43046-025-00272-4

PMID:40289230

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.

摘要

背景

阿糖胞苷是一种前体药物，通过一系列磷酸化步骤被激活为三磷酸阿糖胞苷（Ara-CTP）。为了实现大量白血病细胞死亡，需要高水平的Ara-CTP。含无菌α基序和组氨酸-天冬氨酸结构域蛋白1（SAMHD1）和核苷二磷酸激酶-2（NME2）是参与Ara-CTP代谢的基因。据我们所知，尚无类似研究聚焦于参与阿糖胞苷（Ara-C）代谢的不同多态性与埃及成年急性髓系白血病（AML）患者诱导化疗反应之间的关联。因此，本研究的目的是确定在基于阿糖胞苷的诱导治疗后，SAMHD1基因rs28372906和NME2基因rs3744660多态性对埃及成年AML患者的完全缓解率（CR）、总生存期（OS）和无病生存期（DFS）的影响。

方法

本研究是在埃及开罗大学国家癌症研究所进行的一项回顾性研究。患者组包括136例新诊断的成年AML患者，对照组包括48名健康受试者。所有研究患者的临床病史均从患者记录中收集。使用Taq Man基因分型检测法和Taq Man基因分型预混试剂盒（货号：4,371,353，美国应用生物系统公司）对患者和对照进行NEM2（rs3744660）和SAMHD1（rs28372906）基因分型。在赛默飞世尔Quant Studio™ 3上进行实时聚合酶链反应检测。使用社会科学统计软件包第21.0版分析我们的数据。