Molecular pathogenesis of multiple myeloma and its premalignant precursor
Top Cited Papers
Open Access
- 1 October 2012
- journal article
- review article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 122 (10), 3456-3463
- https://doi.org/10.1172/jci61188
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.This publication has 79 references indexed in Scilit:
- Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacyBlood, 2012
- Multiple MyelomaThe New England Journal of Medicine, 2011
- Pathogenesis of MyelomaAnnual review of pathology, 2011
- Pathogenesis of Monoclonal Gammopathy of Undetermined Significance and Progression to Multiple MyelomaSeminars in Hematology, 2011
- Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myelomaHaematologica, 2010
- Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort studyThe Lancet, 2010
- Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective studyBlood, 2009
- The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressorBlood, 2008
- Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumorsBlood, 2005
- Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemiaLeukemia Research, 2000