Zastosowanie sekwencjonowania następnej generacji do oceny heterogenności klonalnej oraz minimalnej choroby resztkowej u chorych na szpiczaka plazmocytowego

Plasma cell myeloma (PCM) is a cancer characterized by proliferation of clonal plasmocytes in the bone marrow or extraosseus organs. Type of molecular events, especially of secondary nature, affects the kinetics of disease progression and its clinical heterogeneity in particular patients. Plasma cell myeloma poses an ideal study model of intraclonal heterogeneity due to the high genetical variety of the tumor clone. The process of intraclonal evolution plays a key role in the cancerous transformation of monoclonal gammapathy of undetermined significance and progression of smouldering multiple myeloma to symptomatic PCM. The existence of various cell subclones affects the efficacy of therapeutic strategies and urges the need of identification of novel risk stratification factors which may allow the personalization and optimization of the therapy. Next generation sequencing is an ideal tool enabling the assessment of clonal PCM evolution. This technique is capable of identifying funding mutations defining the aggressiveness of the cell clone. Additionally, it enables the assessment of minimal residual disease (MRD), which is not achievable with routine diagnostic methods. The results of MRD assessment have so far mainly prognostic significance, however in the near future it is most probable that it will be the basis of therapy personalization. The understanding of how genetic changes contribute to clonal evolution and thereby to resistance of plasma cell myeloma cells, will enable to overcome and prevent the development of refractory disease.