Association of B-Lineage Lymphoblastic Leukaemia Gene Polymorphisms with Poor Prognostic Features.

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.