20-015-00462

The phenotypic characteristics of pediatric B-cell leukemias with genomic rearrangements of alpha chain T-cell receptor.

Tumor disorders including hematological malignancies are socially significant disease all over the world. Acute lymphoblastic leukemia (ALL) has a special place in this context because of extremely high level of successful therapy. The reason of observed success is risk-oriented therapy and high-doze poly chemotherapy strategies. At the moment the main cause of lethality in ALL is therapy-resistant leukemia forms and relapses. One of the reason of relapses is clonal evolution and high level of clonal diversity of leukemic cells. The main reliable method for clonality assessment in ALL is high-throughput sequencing of rearrangements of T- and B-cell receptor genes. The majority of B-ALL have an anomaly – rearrangements of TCR genes which are abnormal for B-cell lineage. Accoording to previous study, these rearrangements are potential markers of leukemic subclones which are formed right after leukemogenic transformation. The purpose of the present project is study of feature of clonal structure formation in pediatric B-ALL and analysis of influence of abnormal for B-cell TCR alpha chain rearrangements on this process. During this project the previously not analyzed in B-ALL alpha chains of TCR will be detected. The frequency of leukemic TRA rearrangements will be measured in onset as well as in relapse. Furthermore, phenotype characteristics of TRA containing leukemic clones will be identified. The basic knowledge received in this sudy will enrich existing theory of the influence of clonal diversity of leukemic cells on the progression of leukemia and will became a basis for basis for new diagnostics tools.

January 6, 2020 — December 31, 2022

Komkov A.Y. (PI)

Laboratory of comparative and functional genomics

Grant, RFBR

List of publications

  1. Smirnova AO, Miroshnichenkova AM, Olshanskaya YV, Maschan MA, Lebedev YB, Chudakov DM, Mamedov IZ, Komkov A (2023). The use of non-functional clonotypes as a natural calibrator for quantitative bias correction in adaptive immune receptor repertoire profiling. Elife 12,