Vol 6, No 3 (2015)
Review paper
Published online: 2015-12-29

open access

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The etiology and pathogenesis of plasma cell myeloma

Elżbieta Iskierka-Jażdżewska, Krzysztof Jamroziak
DOI: 10.5603/Hem.2015.0037
Hematologia 2015;6(3):245-263.

Abstract

Plasma cell myeloma (PCM) is a neoplasm of plasma cells characterized by specific end organ damage. Despite significant progress in the therapy of PCM, knowledge about the etiopathogenesis of this disease remains unsatisfactory. Monoclonal gammopathy of undetermined significance (MGUS), advanced age, male gender and ethnic group belong to best documented factors associated with an increased risk of PCM development. Several stages of PCM evolution from early and asymptomatic MGUS to symptomatic PCM and final stage of plasma cell leukemia were identified. The current model of PCM pathogenesis assumes the existence of two separate pathways initiating neoplastic transformation – the translocations involving immunoglobulin genes and hyperdiploidy (trisomies). Besides molecular changes within atypical plasma cells, interaction with the bone marrow microenvironment plays a key role in the pathogenesis of PCM. After initial transformation, a number of secondary molecular alterations occur at subclonal level leading to gradual independence from bone marrow microenvironment and increase of the aggressiveness of the tumor. It is likely that better understanding of complex mechanisms of PCM pathogenesis will contribute to development of novel therapeutic strategies and further improvement of PCM prognosis in the future.




Hematology in Clinical Practice