Abstract
Introduction. This review is devoted to the problem of the pathogenesis of pain syndrome in multiple myeloma (MM). The severity of pain often correlates poorly with the plasma cell burden but is highly dependent on tumor aggressiveness determined by primary genetic events.
The aim of this review was to analyze the molecular genetic mechanisms underlying pain syndrome in MM, focusing on how primary chromosomal abnormalities and clonal evolution influence osteolysis and the clinical presentation of bone pain.
Material and Methods. The review was prepared using sources from international (Scopus, Web of Science, PubMed) and the Russian eLIBRARY.ru databases for the period 2020–2025.
Main Points. The pathogenesis of bone pain in MM includes increased intraosseous pressure, release of chemical mediators, formation of microfractures, and tumor interaction with the bone microenvironment. Genetically, MM is divided into hyperdiploid (standard risk) and non-hyperdiploid (high risk) types. High-risk abnormalities, including translocations t(4;14), t(14;16), t(14;20) and deletion del(17p), are associated with aggressive osteolysis and severe pain syndrome. These mutations disrupt the regulation of the RANKL/RANK/OPG system (e.g., c-MAF directly activates RANKL), suppress osteoblastogenesis via DKK1 (in t(4;14)), or cause uncontrolled tumor growth (with TP53 loss). Additionally, pain is amplified by hypoxia (HIF-1α), acidosis (TRPV1 activation), adhesion molecules (VCAM-1/VLA-4), and matrix metalloproteinases (MMP-2, MMP-9). The hyperdiploid type of MM is characterized by a standard RANKL/OPG imbalance and a more «classic,» less aggressive pattern of osteolysis.
Conclusion. Primary genetic events in multiple myeloma determine not only the prognosis of the disease but also the specific pathogenesis of osteolysis, which ultimately shapes a unique pain syndrome profile for each patient. Consideration of the cytogenetic status (e.g., according to the mSMART 3.0 classification) is necessary not only for predicting response to therapy but also for developing personalized pain management strategies.
Authors and affiliations
https://elibrary.ru/qsapty
I.D. Korolenko(1), E.A. Gerashchenko(1), E.S. Kovalenko(1), A.A. Amdiev(1, 2), T.S. Korolenko(2), E.S. Ageeva(1),
1-Order of the Red Banner of Labour Medical Institute named after S.I. Georgievsky, Federal State Autonomous
Educational Institution “V.I. Vernadsky Crimean Federal University”, Lenin Boulevard, 5/7, Simferopol, 295051,
Russian Federation; 2-State Budgetary Healthcare Institution of the Republic of Crimea “N.A. Semashko
Republican Clinical Hospital”, Kievskaya Street, 69, Simferopol, 295017, Russian Federation
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