MOLECULAR GENETIC STRUCTURE OF MULTIPLE MYELOMA TUMOUR CELLS PRIOR TO TREATMENT AND AT THE TIME OF RELAPSE: SHORT REVIEW AND CASE REPORT

Introduction. Multiple myeloma (MM) is a lymphoproliferative disorder, for which the duration of remission is hard to predict.

Aim. To analyse the molecular genetic status of the tumour of MM patient with a short remission period at the onset and relapse of the disease, as well as to conduct its comparison with the clinical course of the disease.

Materials and methods. Somatic mutations were detected through Sanger sequencing. The level of gene expression was analysed using RNA sequencing on the Illumina platform. In order to study chromosomal rearrangements, the authors performed fluorescence hybridisation in situ (FISH study).

Results. Prior to the treatment and during the relapse of the disease, the patient revealed a heterozygous clonal mutation p.182A>C (p.Q61P) in the N-RAS gene, which is known to hamper regulation of the MAPK signalling pathway. The transcriptome analysis performed using the RNA-seq method revealed a sharp increase in the expression of the IL6 gene during relapse (by 30 times), which could have served as a trigger for the progression of multiple myeloma, given that this cytokine stimulates cell proliferation by activating various signalling pathways (MAPK, JAK- STAT, PI3K). The progression of the disease was also accompanied by an increased expression of key regulatory genes (с-MYC, Notch2, MDM, RAF1, STAT4, mTOR) and a sharp decrease in the expression of immunoglobulin genes, which caused deep immunodeficiency in the patient. A molecular cytogenetic study (FISH) revealed trisomy of chromosomes 5, 9 and 15 at the onset of the disease. Disease relapse occurred with the amplification of the 1q21 locus, with hyperdiploidy being preserved.

Conclusion. In order to predict the duration of the remission period, a complex molecular genetic screening is required. 

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