Clonal architecture of leukemic cells and their evolution in pediatric hemoblastosis

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. According to modern concepts, leukemia develops from the precursor lymphatic cells, which, by accumulating mutations, are transformed into leukemia cells that affect the patient's bone marrow and then other organs. Depending on the individual characteristics of ALL progression, both a single leukemic clone and several subclones may form in the bone marrow. Initial clonal heterogeneity may be a key factor in ensuring the survival of leukemic cells during therapy, ultimately leading to relapse. The main objective of the project is the complex study of characteristics of clonal diversity formation and evolution of leukemic cells in B- and T-lineage acute lymphatic leukemia in children. In the course of the project implementation a high-performance multiplex method will be developed, which will allow to reconstruct clonal architecture of leukemic cells simultaneously for hundreds of patients with unprecedented low costs. Using the developed method a large-scale complex analysis of clonal structures of children's T- and B-ALL at the single-cell level will be performed for the first time. To analyze the clonal architecture of leukemic cells, genomic rearrangements of all existing T- and B-cell receptor genes, including previously unanalyzed TRA loci, will be analyzed simultaneously for the first time, which will allow obtaining previously inaccessible accuracy in determining clonal structures of leukemia cells. In addition, the analysis of leukemic cells transcriptomes will be performed to find genetic factors underlying the formation of ALL clonal diversity.

July 1, 2020 — June 30, 2023

Komkov A.Y. (PI)

Laboratory of comparative and functional genomics

Grant, RSF

List of publications

  1. Semchenkova A, Mikhailova E, Komkov A, Gaskova M, Abasov R, Matveev E, Kazanov M, Mamedov I, Shmitko A, Belova V, Miroshnichenkova A, Illarionova O, Olshanskaya Y, Tsaur G, Verzhbitskaya T, Ponomareva N, Bronin G, Kondratchik K, Fechina L, Diakonova Y, Vavilova L, Myakova N, Novichkova G, Maschan A, Maschan M, Zerkalenkova E, Popov A (2022). Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy. Int J Mol Sci 23 (7),
  2. Tirtakusuma R, Szoltysek K, Milne P, Grinev V, Ptasinska A, Chin PS, Meyer C, Nakjang S, Hehir-Kwa JY, Williamson D, Cauchy P, Keane P, Assi SA, Ashtiani M, Kellaway SG, Imperato MR, Vogiatzi F, Schweighart-James EK, Lin S, Wunderlich M, Stutterheim J, Komkov A, Zerkalenkova E, Evans P, McNeill HV, Elder A, Martínez-Soria N, Fordham SE, Shi Y, Russell LJ, Pal D, Smith AG, Kingsbury Z, Becq J, Eckert C, Haas OA, Carey P, Bailey S, Skinner R, Miakova N, Collin M, Bigley V, Haniffa M, Marschalek R, Harrison CJ, Cargo CA, Schewe DM, Olshanskaya Y, Thirman MJ, Cockerill PN, Mulloy JC, Blair HJ, Vormoor HJ, Allan JM, Bonifer C, Heidenreich O, Bomken SN (2022). Epigenetic regulator genes direct lineage switching in MLL/AF4 leukaemia. Blood 140 (17), 1875–1890
  3. Mikhailova E, Illarionova O, Komkov A, Zerkalenkova E, Mamedov I, Shelikhova L, Olshanskaya Y, Miakova N, Novichkova G, Karachunskiy A, Maschan M, Popov A (2022). Reliable Flow-Cytometric Approach for Minimal Residual Disease Monitoring in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia after CD19-Targeted Therapy. Cancers (Basel) 14 (21),
  4. 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,
  5. Smirnova AO, Miroshnichenkova AM, Belyaeva LD, Kelmanson IV, Lebedev YB, Mamedov IZ, Chudakov DM, Komkov AY (2023). Novel bimodal TRBD1-TRBD2 rearrangements with dual or absent D-region contribute to TRB V-(D)-J combinatorial diversity. Front Immunol 14, 1245175