Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Cancer Chemother Pharmacol. 2021 Aug;88(2):313-321. doi: 10.1007/s00280-021-04290-6. Epub 2021 May 7.
Asparaginase (ASNase) is a key component in the treatment protocols of childhood acute lymphoblastic leukemia (ALL). Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) mediate the anti-leukemic effect of ASNase. Only a few reports studied the association between polymorphisms in these genes and treatment-related toxicity and response. Therefore, the current study aimed to investigate the association of ASNS and ATF5 polymorphisms with the susceptibility to ASNase-related toxicity and disease outcome in a population of childhood ALL Egyptian patients.
In this study, 88 children with ALL were enrolled and genotyped for ASNS T629A and ATF5 C362T polymorphisms using allelic discrimination assay.
The studied polymorphisms did not associate with hypersensitivity or thrombosis, while the ATF5 C362T polymorphism was associated significantly with decreased ASNase-associated pancreatitis (AAP) risk under the dominant model. Patients carrying TT/CT genotypes of ATF5 C362T polymorphism had a significantly better overall survival (OS) and longer event-free survival (EFS) compared to patients with CC genotype. Multivariate analysis confirmed the independent prognostic value of the ATF5 C362T dominant model.
ATF5 362TT and CT genotypes were associated with decreased risk to develop AAP and better disease outcome demonstrating a low risk for events and superior survival.
天冬酰胺酶（ASNase）是儿童急性淋巴细胞白血病（ALL）治疗方案的关键组成部分。天冬酰胺合成酶（ASNS）和碱性亮氨酸拉链激活转录因子 5（ATF5）介导 ASNase 的抗白血病作用。只有少数报道研究了这些基因的多态性与治疗相关毒性和反应之间的关系。因此，本研究旨在探讨 ASNS 和 ATF5 多态性与埃及儿童 ALL 患者对 ASNase 相关毒性和疾病结局易感性的关系。
本研究纳入了 88 例 ALL 患儿，并使用等位基因鉴别检测法对 ASNS T629A 和 ATF5 C362T 多态性进行了基因分型。
研究的多态性与过敏或血栓形成无关，而 ATF5 C362T 多态性在显性模型下与降低 ASNase 相关胰腺炎（AAP）风险显著相关。携带 ATF5 C362T 多态性 TT/CT 基因型的患者总生存（OS）和无事件生存（EFS）明显优于 CC 基因型患者。多变量分析证实了 ATF5 显性模型的独立预后价值。
ATF5 362TT 和 CT 基因型与降低发生 AAP 的风险和更好的疾病结局相关，表明事件风险低，生存状况较好。
