DOI: https://doi.org/10.20535/ibb.2018.2.4.143938

Results of Cytogenetic and Molecular Cytogenetic Studies in Relapce/Refractory of Multiple Myeloma

Svitlana Andreieva, Kateryna Korets

Abstract


Background. Multiple myeloma (MM) – a tumor of the lymphoid tissue, which is characterized by low proliferative activity of abnormal cells and a wide range of acquired chromosomal aberrations that play a leading role in predicting the course of the disease. Accumulation of new data in the relapsed/refractory of MM will make it possible to understand the nature of the formation of cloning insensitive to chemotherapy (CT), to predict the effectiveness of therapy, which will further improve the individualization of treatment for each patient.

Objective. The aim of the study is to determine the peculiarities of chromosomal aberrations of abnormal clones of bone marrow (BM) cell in relapsed/refractory of MM by standard cytogenetic and molecular cytogenetic investigations.

Methods. Analysis of BM cells chromosomal abnormalities in relapsed/refractory of MM for 62 patients with MM was performed. Slides of metaphase chromosomes were prepared according to standard procedure after cultivating during 24 or 96 h in the medium without stimulation.

Results. Clonal chromosomal abnormalities were formed, complexity structure of karyotypes with clone structures was shown. In structural rearrangements, derivative chromosomes (34.9%) and balanced translocations (23.2%) were dominated at cytogenetic procedure. By molecular cytogenetic (i-FISH) investigation chromosomal abnormalities were detected in 26.7% cases. Del(17)(p13.1) was registered in 22.0%. Aberrations involving IGH were fixed in 5.7%. The atypical signal distribution determined by i-FISH may indicate another possible mechanism for the evolution of an abnormal clone.

Conclusions. The cytogenetic peculiarities of the formation of abnormal BM cell clones in relapse/refractory of MM formations, discovered by us, supplement the understanding of the biological features of the disease and contribute to the outline of further tasks for the study of genetic aberrations in MM.

Keywords


Multiple myeloma; Relapse/refractory; Bone marrow cells; Chromosomal abnormality heterogeneity

References


Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48. DOI: 10.1016/S1470-2045(14)70442-5

Kaufman GP, Gertz MA, Dispenzieri A, Lacy MQ, Buadi FK, Dingli D, et al. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma. Leukemia. 2016 Mar;30(3):633-9. DOI: 10.1038/leu.2015.287

Rajan AM, Rajkumar SV. Interpretation of cytogenetic results in multiple myeloma for clinical practice. Blood Cancer J. 2015 Oct;5(10):e365. DOI: 10.1038/bcj.2015.92

Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016 Jul;91(7):719-34. DOI: 10.1002/ajh.24402

Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, et al. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the Intergroupe Francophone du Myélome Experience. J Clin Oncol. 2013 Aug;31(22):2806-09. DOI: 10.1200/JCO.2012.46.2598

Gozzetti A, Frasconi A, Crupi R. Molecular cytogenetics of multiple myeloma. Austin J Cancer Clin Res. 2014 Dec;1(4):1020.

Jekarl DW, Min CK, Kwon A, Kim H, Chae H, Kim M, et al. Impact of genetic abnormalities on the prognoses and clinical parameters of patients with multiple myeloma. Ann Lab Med. 2013 Jul;33(4):248-54. DOI: 10.3343/alm.2013.33.4.248

Liu J, Yang H, Liang X, Wang Y, Hou J, Liu Y, et al. Meta-analysis of the efficacy of treatments for newly diagnosed and relapse/refractory multiple myeloma with del(17p). Oncotarget. 2017;8:62435-44. DOI: 10.18632/oncotarget.18722

Weinhold N, Ashby C, Rasche L, Chavan SS, Stein C, Stephens OW, et al. Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood. 2016;128(13):1735-44. DOI: 10.1182/blood-2016-06-723007

Chavan SS, He J, Tytarenko R, Deshpande S, Patel P, Bailey M, et al. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker. Blood Cancer J. 2017;7(2):e535. DOI: 10.1038/bcj.2017.12

Avet-Loiseau H, Durie BG, Cavo M, Attal M, Gutierrez N, Haessler J, et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia. 2013 Mar;27(3):711-7. DOI: 10.1038/leu.2012.282

Sonneveld P, Broijk A. Treatment of relapsed and refractory multiple myeloma. Haematologica. 2016 Apr;101(4):396-406. DOI: 10.3324/haematol.2015.129189

Rooney DE, Czepulkovsky BH. Human cytogenetics. A practical approach. Malignancy and acquired abnormalities. 2nd ed. Oxford, New York, Tokyo: IRL Press at Oxford University Press; 1995. 293 p.

McGowan-Jordan J, Simons A, Schmid M. An international system for human cytogenetic nomenclature. Recommendations of the International Standing Committee on Нuman Cytogenomic Nomenclature. Karger; 2016. 140 p.

Korets KV, Ruzhinska OE, Skorohod IM, Karnabeda OA, Korenkova ІМ, Andreieva SV. Peculiarities of chromosomal abnormalities in bone marrow cells at diagnosis of multiple myeloma. Likars'ka Sprava. 2017;8:70-9.

Chin M, Sive JI, Allen C, Roddje C, Chavda SJ, Smith D, et al. Prevalence and timing of TP53 mutations in del(17p) myeloma and effect on survival. Blood Cancer J. 2017 Sep;7(9):e610. DOI: 10.1038/bcj.2017.76

Hebraud B, Caillot D, Corre J, Marit G, Hulin C, Leleu X, et al. Lost and gain of t(4;14) and t(11;14) in multiple myeloma patients between relapse and diagnosis: an illustration of clonal dynamic during disease course. An IFM Study. Blood. 2012 Oct;120(21):196.


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