Bazarbayeva Aigul, Manzhuova Lyazat, Svyatova Gulnara, Berezina Galina, Sarsekbayeva Farida, Kamalova Diana
Department of Science and Postgraduate Education, Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan.
Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan.
Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4339-4349. doi: 10.31557/APJCP.2024.25.12.4339.
Of this study was to analyse the correlation of gene polymorphisms with clinical and laboratory data of paediatric patients with B-lineage acute lymphoblastic leukaemia with prognostically unfavourable features.
A study of 200 children with B-lineage acute lymphoblastic leukaemia (B-ALL) treated with polychemotherapy programmes was conducted. Analysis by sex revealed a statistically insignificant predominance of the group of boys over girls (54%). The mean age of the subjects was 9.3±0.2 years. Genotyping of polymorphic loci was performed using TaqMan method of single site-specific amplification and genotyping. The data of patients with initial prognostically unfavourable clinical and laboratory data in the form of initial leukocytosis from 50 to 99 thousand - 10 (5%), over 100 thousand - 16 (8%), initial CNS lesion in the form of neuroleukaemia - 5 (2.5%), initial splenomegaly more than 6 cm - 12 (6%); patients with poor response to therapy, having absolute number of blast cells in peripheral blood over 1,000 on day 8 of treatment according to the protocol (response to prednisolone prophase) - 13 (7%), with unsatisfactory response to treatment on Day 15 - 40 patients (20%) and on Day 33 - 4 children (2%); also patients who developed relapse of the disease - 17 (9%).
According to the findings, of all 24 gene variants, 13 variants (54%), namely, HLA - rs6457327, TNF - rs1800630 and rs2229094, GATA3 - rs3824662, TP53 - rs1042522, CASP9 - rs4661636, CASP8 - rs10505477, CEBPE - rs2239633; PIP4K2A - rs7088318, CASC8 - rs10505477, IRF4 - rs87207, CYP1A1 - rs4646903 and rs7089424 of ARID5B gene were found to be associated with B-ALL and unfavourable prognostic features.
The findings of this study revealed significant associations of polymorphic genetic variants, which may serve as a basis for the development of effective methods for predicting the risk of relapse development and the timeliness of intensification of B-ALL treatment. Prompt genetic counselling of children with identified unfavourable genotypes of the investigated gene polymorphisms will make it possible to predict the development of relapse, resistance and/or poor response to B-ALL treatment, and to propose an individual strategy for monitoring children's health in the short and long term.
本研究旨在分析基因多态性与具有预后不良特征的B系急性淋巴细胞白血病儿科患者的临床及实验室数据之间的相关性。
对200例接受多药化疗方案治疗的B系急性淋巴细胞白血病（B-ALL）儿童进行了研究。按性别分析显示，男孩组比女孩组略占优势，但无统计学意义（54%）。受试者的平均年龄为9.3±0.2岁。使用单位点特异性扩增和基因分型的TaqMan方法对多态性位点进行基因分型。研究对象包括初始白细胞增多（50000至99000 - 10例（5%），超过100000 - 16例（8%））、以神经白血病形式出现的初始中枢神经系统病变 - 5例（2.5%）、初始脾肿大超过6cm - 12例（6%）等具有初始预后不良临床和实验室数据的患者；治疗反应不佳的患者，即根据方案在治疗第8天外周血原始细胞绝对数超过1000（对泼尼松龙前期的反应） - 13例（7%），在第15天治疗反应不满意 - 40例（20%），在第33天 - 4例（2%）；以及疾病复发的患者 - 17例（9%）。
根据研究结果，在所有24个基因变异中，发现13个变异（54%），即HLA-rs6457327、TNF-rs1800630和rs2229094、GATA3-rs3824662、TP53-rs1042522、CASP9-rs4661636、CASP8-rs10505477、CEBPE-rs2239633；PIP4K2A-rs7088318、CASC8-rs10505477、IRF4-rs87207、CYP1A1-rs4646903以及ARID5B基因的rs7089424与B-ALL及不良预后特征相关。
本研究结果揭示了多态性基因变异之间的显著关联，这可为开发预测B-ALL复发风险和强化治疗及时性的有效方法奠定基础。对具有所研究基因多态性不良基因型的儿童进行及时的遗传咨询，将有助于预测B-ALL治疗中复发、耐药和/或反应不佳情况的发生，并提出短期和长期监测儿童健康的个体化策略。
