Biopolym. Cell. 2022; 38(1):17-25.
Expression of chimeric genes in bone marrow cells of children with acute lymphoblastic leukemia upon cytostatic therapy
1Vynnytska O. A., 1Dubey L. Ya.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010


Aim. To study the expression of chimeric genes in bone marrow cells as prognostic factors of the course of acute lymphoblastic leukemia (ALL) in children and evaluate their role in resistance to cytostatic chemotherapy. Methods. The AF4-MLL, BCR-ABL, E2A-RVX, TEL-AML1 chimeric gene expression level was determined by RT-qPCR. Results. The AF4-MLL oncogene was not expressed in children during remission, and the expression of all other studied oncogenes was at a low level. In conditions of relapse, there was no expression of the TEL-AML oncogene and a high expression of the BCR-ABL. Conclusions. The development, course, and survival of all patients largely depend on the expression of AF4-MLL, BCR-ABL, E2A-PBX1, TEL-AML chimeric genes in the bone marrow; this should be taken into account when detecting early relapses in patients after chemotherapy.
Keywords: acute lymphoblastic leukemia, oncogene, AF4-MLL, BCR-ABL, E2A-PBX, TEL-AML


[1] Moorman AV. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia. Haematologica. 2016; 101(4):407-16.
[2] Lopes BA, Barbosa TC, Souza BKS, Poubel CP, Pombo-de-Oliveira MS, Emerenciano M. IKZF1 Gene in childhood B-cell precursor acute lymphoblastic leukemia: interplay between genetic susceptibility and somatic abnormalities. Cancer Prev Res (Phila). 2017; 10(12):738-744.
[3] Kiem HT, Nhu HP, Kim HNT, Van HC. Causes of death in childhood acute lymphoblastic leukemia at hue central hospital for 10 years (2008-2018). Glob Pediatr Health. 2020; 7:2333794X20901930.
[4] Goto H. Childhood relapsed acute lymphoblastic leukemia: Biology and recent treatment progress. Pediatr Int. 2015; 57(6):1059-66.
[5] Yokota T, Kanakura Y. Genetic abnormalities associated with acute lymphoblastic leukemia. Cancer Sci. 2016; 107(6):721-5.
[6] DeAngelo DJ, Jabbour E, Advani A. Recent advances in managing acute lymphoblastic leukemia. Am Soc Clin Oncol Educ Book. 2020; 40:330-342.
[7] Britten O, Ragusa D, Tosi S, Kamel YM. MLL-rearranged acute leukemia with t(4;11)(q21;q23)-current treatment options. Is there a role for CAR-T cell therapy? Cells. 2019; 8(11):1341.
[8] Pi WC, Wang J, Shimada M, Lin JW, Geng H, Lee YL, Lu R, Li D, Wang GG, Roeder RG, Chen WY. E2A-PBX1 functions as a coactivator for RUNX1 in acute lymphoblastic leukemia. Blood. 2020; 136(1):11-23.
[9] Ajuba IC, Madu AJ, Okocha C, Ibegbulam OG, Okpala I, Nna OE. Frequency and clinical impact of ETV6/RUNX1, AF4-MLL, and BCR/ABL fusion genes on features of acute lymphoblastic leukemia at presentation. Niger J Clin Pract. 2016; 19(2):237-41.
[10] Lilleyman JS, Hann IM, Stevens RF, Eden OB, Richards SM. French American British (FAB) morpho-logical classification of childhood lymphoblastic leukaemia and its clinical importance. J Clin Pathol. 1986; 39(9): 998-1002.
[11] Koh CM. Isolation of genomic DNA from mammalian cells. Methods Enzymol. 2013; 529:161-9.
[12] Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using realtime quantitative PCR and the 22DDCT method. Methods. 2001; 25: 402-8.
[13] Takahashi S, Yokoyama A. The molecular functions of common and atypical MLL fusion protein com-plexes. Biochim Biophys Acta Gene Regul Mech. 2020; 1863(7):194548.
[14] Tasian SK, Loh ML, Hunger SP. Philadelphia chromosome-like acute lymphoblastic leukemia. Blood. 2017; 130(19):2064-2072.
[15] Vinhas R, Lourenço A, Santos S, Lemos M, Ribeiro P, de Sousa AB, Baptista PV, Fernandes AR. A novel BCR-ABL1 mutation in a patient with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. Onco Targets Ther. 2018; 11:8589-8598.
[16] Cuellar S, Vozniak M, Rhodes J, Forcello N, Olszta D. BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia. J Oncol Pharm Pract. 2018; 24(6):433-452.
[17] Hong Y, Zhao X, Qin Y, Zhou S, Chang Y, Wang Y, Zhang X, Xu L, Huang X. The prognostic role of E2A-PBX1 expression detected by real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) in B cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell trans-plantation. Ann Hematol. 2018; 97(9):1547-1554.
[18] Ketsa OV, Marchenko MM. Free radical oxidation in liver mitochondria of tumor-bearing rats and its correction by essential lipophilic nutrients. Ukr Biochem J. 2020; 92(1):127-134.
[19] Kantner HP, Warsch W., Delogu A, Bauer E, Esterbauer H, Casanova E, Sexl V, Stoiber D. ETV6/RUNX1 induces reactive oxygen species and drives the accumulation of DNA damage in B cells. Neoplasia. 2013; 15(11):1292-300.
[20] Rose-James A, Shiji R, Kusumakumary P, Nair M, Suraj KG, Sreelekha TT. Profiling gene mutations, translocations, and multidrug resistance in pediatric acute lymphoblastic leukemia: a step forward to personalizing medicine. Med Oncol. 2016; 33(9):98.