Document Type : Research Articles
Authors
1
Department of Science and Postgraduate Education, Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan.
2
Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan.
3
Republican Medical and Genetic Counselling Centre, Scientific Center for Obstetrics, Gynecology and Perinatology, Almaty, Republic of Kazakhstan.
4
Department of Strategic Development and Science, Scientific Center for Obstetrics, Gynecology and Perinatology, Almaty, Republic of Kazakhstan.
5
Department of Biostatistics, Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan.
Abstract
Objective: 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. Methods: 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%). Results: 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. Conclusions: 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.
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