Molecular pathogenesis of multiple myeloma and its premalignant precursor

W. Michael Kuehl, Peter Leif Bergsagel

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Multiple myeloma is a monoclonal tumor of plasma cells, and its development is preceded by a premalignant tumor with which it shares genetic abnormalities, including universal dysregulation of the cyclin D/retinoblastoma (cyclin D/RB) pathway. A complex interaction with the BM microenvironment, characterized by activation of osteoclasts and suppression of osteoblasts, leads to lytic bone disease. Intratumor genetic heterogeneity, which occurs in addition to intertumor heterogeneity, contributes to the rapid emergence of drug resistance in high-risk disease. Despite recent therapeutic advances, which have doubled the median survival time, myeloma continues to be a mostly incurable disease. Here we review the current understanding of myeloma pathogenesis and insight into new therapeutic strategies provided by animal models and genetic screens.

Original languageEnglish (US)
Pages (from-to)3456-3463
Number of pages8
JournalJournal of Clinical Investigation
Volume122
Issue number10
DOIs
StatePublished - Oct 1 2012

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Multiple Myeloma
Cyclin D
Plasmacytoma
Genetic Heterogeneity
Retinoblastoma
Bone Diseases
Osteoclasts
Osteoblasts
Drug Resistance
Animal Models
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Molecular pathogenesis of multiple myeloma and its premalignant precursor. / Kuehl, W. Michael; Bergsagel, Peter Leif.

In: Journal of Clinical Investigation, Vol. 122, No. 10, 01.10.2012, p. 3456-3463.

Research output: Contribution to journalArticle

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