11q23/MLL rearrangements in adult acute leukemia
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-3.16495Keywords:
11q23/MLL rearrangements, acute leukemia., cytogenetic abnormalities, diagnosis, karyotype, prognosisAbstract
Summary. Aim: To detect the frequency, diagnostic and prognostic significance of 11q23/MLL rearrangements and to determine the chromosomes that are most frequently involved in 11q23/MLL abnormalities in adult acute leukemia (AL). Materials and Methods: Cytogenetic investigations of bone marrow and/or peripheral blood cells from 140 patients with acute myeloid leukemia (AML) and 57 patients with acute lymphoblastic leukemia (ALL) were performed. The methods of conventional cytogenetics (GTG-banding) and fluorescence in situ hybridization were used. Results: Chromosomal abnormalities in leukemia cells were found by conventional cytogenetic methods in 80 (57%) and 37 (65%) adult patients with AML and ALL, respectively. 11q23/MLL rearrangements were found in 7 (5%) and 8 (14%) patients with AML and ALL, respectively. Among them, 8 (53.4%) patients had translocations, 2 (13.3%) — had deletions and 5 (33.3%) patients had trisomies or tetrasomies of chromosome 11. With respect to the distribution of partner chromosomes involved in 11q23/MLL translocations chromosome 4 was found to participate in 3 (37.5%) cases of 11q23/MLL translocations, 9 — in 2 (25%) cases and chromosomes 10, 14 and non-identified chromosome were involved in 1 (12.5%) case each. Nine patients (60%), besides abnormal ones, had 9–86% normal metaphases in their karyotypes. Of 15 patients with 11q23/MLL rearrangements, 5 (33%) patients had only 11q23/MLL rearrangements, whereas other 10 (67%) — had additional cytogenetic abnormalities, besides 11q23/MLL rearrangements. Conclusions: Chromosomal abnormalities of various kinds were found in 57% and 65% adult patients with AML and ALL, respectively. The frequency of 11q23/MLL rearrangements in patients with AML and ALL was 5% and 14%, respectively. Since AL patients with 11q23/MLL rearrangements are attributed to cytogenetic categories of AL with a poor or intermediate risk prognosis, cytogenetic methods should be included in the standard examination of AL patients for diagnosis, prognosis and selection of the optimal treatment strategy.
References
Bain BJ. Leukaemia Diagnosis. 5 ed. NY: Wiley-Blackwell, 2017. 559 p. https://doi.org/10.1111/bjh.16351.
Heim S, Mitelman F. Cancer Cytogenetics. 4 ed. NY: Wiley-Blackwell, 2015. 648 p. https://doi.org/10.1002/9781118795569.
Liang K, Volk A, Haug J, et al. Therapeutic targeting of MLL degradation pathways in MLL-rearranged leukemia. Cell 2017; 168: 59–72. https://doi.org/10.1016/j.cell.2016.12.011.
Cox M, Panetta P, Lo-Coco F, et al. Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation. Am J Clin Pathol 2004; 122: 298–306. https://doi.org/10.1309/RX27R8GJQM330C22.
Meyer C, Burmeister T, Groger D, et al. The MLL recombinome of acute leukemias in 2017. Leukemia 2018; 32: 273–84. https://doi.org/10.1038/leu.2017.213.
Ilencikova D, Kolenova A. MLL gene alterations in acute myeloid leukemia (11q23/MLL+ AML). In: Siregar Y, ed. Oncogene and Cancer — From Bench to Clinic. IntechOpen, 2013: 225–46. https://doi.org/10.5772/55141.
Andreyeva SV, Drozdova VD. Standard of Analysis of Chromosome Preparations in Hematopoietic Neoplasms (Guidelines). Kyiv, 2007. 44 p. (in Ukrainian).
Wan TSK. Cancer Cytogenetics. Methods and Protocols. Methods in Molecular Biology. NY: Humana Press, 2017. 340 p. https://doi.org/10.1007/978-1-4939-6703-2.
Haferlach C, Rieder H, Lillington D, et al. Proposals for standardized protocols for cytogenetic analyses of acute leukemias, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disorders, and myelodysplastic syndromes. Genes Chromosomes Cancer 2007; 46: 494–9. https://doi.org/10.1002/gcc.20433.
Rack KA, van den Berg E, Haferlach C. Cytogenetics and molecular genetics European recommendations and quality assurance for cytogenomic analysis of hematological neoplasms. Leukemia 2019; 33: 1851–67. https://doi.org/10.1038/s41375-019-0378-z.
McGowan-Jordan J, Simons A, Schmid M. An International System for Human Cytogenetic Nomenclature. Basel: S. Karger, 2016. 140 p. https://doi.org/10.1159/isbn.978-3-318-06861-0.
Pinkel D, Straume T, Gray JW. Cytogenetic analysis using quantitative high sensitivity, fluorescence hybridization. Proc Natl Acad Sci USA 1986; 83: 2934–8. https://doi.org/10.1073/pnas.83.9.2934.
Olshanskaya YuV, Domracheva EV. Chromosomal Rearrangements in Acute Leukemias. Moscow: MEDpress-inform, 2006. 122 p. (in Russian).
Yokoyama A. Molecular mechanisms of MLL-associated leukemia. Int J Hematol 2015; 101: 352–61. https://doi.org/10.1007/s12185-015-1774-4.
Wang KC, Helms JA, Chang HY. Regeneration, repair and remembering identity: the three Rs of Hox gene expression. Trends Cell Biol 2009; 19: 268–75. https://doi.org/10.1016/j.tcb.2009.03.007.
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–405. https://doi.org/10.1182/blood-2016-03-643544.
Mrozek K, Marcucci G, Nicolet D, et al. (2012). Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol 2012; 30: 4515–23. https://doi.org/10.1200/JCO.2012.43.4738.
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