Molecular pathogenesis of multiple myeloma and its premalignant precursor

W. Michael Kuehl, P. Leif Bergsagel

Research output: Contribution to journalReview articlepeer-review

222 Scopus citations


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
Issue number10
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Medicine(all)


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