Molecular pathogenesis of multiple myeloma and its premalignant precursor
WM Kuehl, PL Bergsagel - The Journal of clinical …, 2012 - Am Soc Clin Investig
WM Kuehl, PL Bergsagel
The Journal of clinical investigation, 2012•Am Soc Clin InvestigMultiple 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 …
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 …
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.
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