Prospects of the development of the mutation status in children with acute lymphoblastic leukemia

October 9, 2018
834
Resume

Objectives — to determine the potential of stratification of children with acute lymphoblastic leukemia (ALL) into prognostic groups using molecular genetic diagnostic techniques apart or in combination with other stratification methods. Materials and methods. The analysis of the chosen literature of years 2010–2018 concerning the problems of prognostication of the effectiveness of treatment in children with ALL at initial diagnosis and after relapse has been performed. Results. To use National Cancer Institute classification for stratifying children into prognostic groups is the most simple and effective method. However, according to the development of molecular genetic methods to analyze the mutational status of genes, and according toverity of publications dedicated to new strategies to use mutational status parameters for detailed stratification of children with ALL, the combined approach may improve the accuracy of prognosis of treatment. Currently, the most studied and significant mutations affecting the prognosis of children with ALL are IKZF1, CDKN2A/B, NRAS/ KRAS, TP53 and PAX5 mutations. Moreover, by identifying the characteristics of the ABL1 gene mutations in patients with translocation t(9;22)/BCR-ABL1, it is possible to achieve better treatment of ALL with protein kinase inhibitors by assigning the most effective generation of the drug. The presence of certain mutations can induce tolerance to certain components of standard scheme of treatment. Thus, NR3C1/BTG1 and CREBBP mutations may be associated with resistance to glucocorticoid therapy and NT5C2 — to nucleoside analogues in children with ALL. After the relapse of ALL, the mutational status of the blast cells is different from its characteristics at the stage of primary diagnosis and should be re-determined. Conclusion. The potentially effective approache for the accurate and comprehensive stratification of children with ALL into prognostic groups is the combine standard scheme and mutational status parameters.

Published: 29.10.2018

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