The correlation analysis between the number of blast cells in bone marrow and peripheral blood was performed, and the dependence of blast percentage on the presence of molecular genetic translocations (AF4/MLL, BCR/ABL1, TEL/AML, E2A/PBX1) in patients with acute lymphoblastic leukemia (ALL) under the conditions of ALLIC-BFM 2009 cytostatic therapy was researched. The purpose of the study was to establish a relationship between the number of blast cells in bone marrow and peripheral blood depending on the presence of molecular genetic translocations for early detection of induction treatment by ALLIC BFM 2009. Materials and methods. The survey group consisted of 105 children aged 12 months to 16 years (median age was 6 years). Among those surveyed were 62 boys (59.0%) and 43 girls (41.0%). All patients were diagnosed with acute lymphoblastic leukemia. Results and discussion. Correlation analysis revealed a high degree of correlation between the number of blast cells in the bone marrow and peripheral blood, as the correlation coefficient (r) is 0.87. It is shown that the increase in the number of blast cells depends on the presence of chromosomal translocations. The highest number of blasts was observed in patients with BCR/ABL1 and E2A/PBX1 translocations, in whom the content of blasts in bone marrow was 97 and 96%, respectively, and in peripheral blood - 67 and 73%, respectively. It was found that treatment under the ALLIC BFM 2009 program leads to a decrease in the number of blast cells in the bone marrow and blood with minimal values on the 33rd day of treatment. It has been shown that the highest levels of blast cells during chemotherapy are observed in patients with chromosomal translocations BCR/ABL1 and E2A/PBX1. In patients with AF4/MLL translocation, the efficacy of therapy was the highest because no blast cells in the bone marrow were visualized on day 33 of treatment. The study of the primary response of patients with acute lymphoblastic leukemia to induction treatment according to the ALLIC BFM 2009 program revealed the dependence of the level of blast cells of bone marrow and blood on the type of chromosomal aberration. Patients with BCR/ABL1 and E2A/PBX1 have the highest resistance to chemotherapy with molecular genetic translocations, and patients with AF4/MLL and TEL/AML have the lowest resistance, as evidenced by the presence and absence of blast cells in the peripheral blood, respectively. Conclusion. Establishing the relationship between cytogenetic and molecular genetic features of the tumour clone will help determine the degree of malignancy of the process, as well as the risk group for the course of the disease. Determining the dependence of acute leukemia on molecular genetic translocations will make it possible to further modify the treatment program

Keywords: blast cells, chimeric genes AF4/MLL, BCR/ABL, E2A/PBX1, TEL/AML, translocation, acute lymphoblastic leukemia in children, bone marrow, blood

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1. Chen X, Zheng J, Zou Y, Song C, Hu X, Zhang C. IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells. J Hematol Oncol. 2013 Oct 08; 6(1): 72-82. https://doi.org/10.1186/1756-8722-6-72
2. Chiarini F, Lonetti A, Evangelisti C, Buontempo F, Orsini E, Evangelisti C, et al. Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting. Biochim Biophys Acta. 2016 Mar; 1863(3): 449-463. https://doi.org/10.1016/j.bbamcr.2015.08.015
3. Pui CH, Roberts KG, Yang JJ, Mullighan CG. Philadelphia chromosome-like acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2017 Aug 01; 17(8): 464-470. https://doi.org/10.1016/j.clml.2017.03.299
4. Jain S, Abraham A. BCR-ABL1-like B-acute lymphoblastic leukemia/lymphoma: a comprehensive review. Arch Pathol Lab Med. 2020 Oct 23; 144(2): 150-155. https://doi.org/10.5858/arpa.2019-0194-RA
5. Cernan M, Szotkowski T, Pikalova Z. Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017; 161(3): 234-241. https://doi.org/10.5507/bp.2017.013
6. Agarwal A, Bolosky WJ, Wilson DB, Eide CA, Olson SB, Fan G, et al. Differentiation of leukemic blasts is not completely blocked in acute myeloid leukemia. Proc Natl Acad Sci USA. 2019 Nov 21; 116(49): 24593-24599. https://doi.org/10.1073/pnas.1904091116
7. Mikosik A, Henc I, Ruckemann-Dziurdzińska K, Frąckowiak JE, Płoszyńska A, Balcerska A, et al. Increased μ-calpain activity in blasts of common B-precursor childhood acute lymphoblastic leukemia correlates with their lower susceptibility to apoptosis. PLoS One. 2015 Aug 28; 10(8): e0136615. https://doi.org/10.1371/journal.pone.0136615
8. Garibyan L, Avashia N. Polymerase chain reaction. J Invest Dermatol. 2013 Mar 01; 133(3): 1-4. https://doi.org/10.1038/jid.2013.1
9. Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood. 2017 Jan 19; 129(3): 347-357. https://doi.org/10.1182/blood-2016-07-726307
10. Glier H, Novakova M, Te Marvelde J, Bijkerk A, Morf D, Thurner D, et al. Comments on EuroFlow standard operating procedures for instrument setup and compensation for BD FACS Canto II, Navios and BD FACS Lyric instruments. J Immunol Methods. 2019 Dec; 475: 112680. https://doi.org/10.1016/j.jim.2019.112680
11. Kashiwagi S, Fujioka Y, Kondo T, Satoh AO, Yoshida A, Fujioka M, et al. Localization of BCR-ABL to stress granules contributes to its oncogenic function. Cell Struct Funct. 2019; 44(2): 195-204. https://doi.org/10.1247/csf.19033
12. Sontakke P, Carretta M, Jaques J, Brouwers-Vos AZ, Lubbers-Aalders L, Yuan H, et al. Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model. Leukemia. 2016 Apr 29; 30(10): 2064-2073. https://doi.org/10.1038/leu.2016.108
13. Boer JM, Steeghs EM, Marchante JR, Boeree A, Beaudoin JJ, Beverloo HB, et al. Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia. Oncotarget. 2017; 8(3): 4618-4628. https://doi.org/10.18632/oncotarget.13492
14. Ferreira AF, Moura LG, Tojal I, Ambrósio L, Pinto-Simões B, Hamerschlak N, et al. ApoptomiRs expression modulated by BCR-ABL is linked to CML progression and imatinib resistance. Blood Cells Mol Dis. 2014 Jun-Aug; 53(1-2): 47-55. https://doi.org/10.1016/j.bcmd.2014.02.008
15. Abruzzo LV, Herling CD, Calin GA, Oakes C, Barron LL, Banks HE, et al. Trisomy 12 chronic lymphocytic leukemia expresses a unique set of activated and targetable pathways. Haematologica. 2018 Dec; 103(12): 2069-2078. https://doi.org/10.3324/haematol.2018.190132
16. Messina M, Chiaretti S, Wang J, Fedullo AL, Peragine N, Gianfelici V, et al. Prognostic and therapeutic role of targetable lesions in B-lineage acute lymphoblastic leukemia without recurrent fusion genes. Oncotarget. 2016 Mar 22; 7(12): 13886-901. https://doi.org/10.18632/oncotarget.7356