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Prognostic and predictive role of hereditary genetic variants in multiple myeloma
Kiss Katalin Piroska
Clinical Medicine
Dr. Reusz György
NET, 16. emelet Transzlációs Medicina Intézet könyvtára
2022-04-26 10:00:00
Clinical Haematology
Dr. Masszi Tamás
Dr. Andrikovics Hajnalka
Dr. Istenes Ildikó
Dr. Apáti Ágota
Dr. Vásárhelyi Barna
Dr. Szabó Zsófia
Dr. Kádár Katalin
Félné Dr. Semsei Ágnes
Multiple myeloma is an extremely heterogeneous disease greatly influenced by underlying genetic abnormalities, the tumour and bone marrow microenvironment. The investigation of the genetic background, the identification of new prognostic and predictive biomarkers play an important role not only in risk stratification, but also in selecting the most appropriate therapy for the patient. We analysed the effect of two newly identified polymorphisms in a group of multiple myeloma patients in Hungary. First, we studied the FOPNL single nucleotide polymorphism (rs72773978) identified as a novel adverse prognostic factor which was associated with poor overall survival in myeloma. Next, we investigated PSMB1 rs12717 variant, as a predictive marker influencing bortezomib therapy. In the course of the survival endpoint study of the FOPNL rs72773978 minor allele, the opposite effect was observed for the subgroups based immunomodulatory and bortezomib-based treatments. The analysis of the PSMB1 rs12717 polymorphism revealed shorter progression free survival in myeloma patients carrying the variant allele. Concerning the functional study of the polymorphism, decreased proteolytic activity of proteasomes and decreased inhibitory effect of bortezomib therapy were observed with trypsin-like and caspase-like activities. Our results suggest that the study of different genetic variants may contribute to more precise prognosis estimates and for the application of personalized therapy.