Document Detail


Molecular pathogenesis of multiple myeloma and its premalignant precursor.
MedLine Citation:
PMID:  23023717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
W Michael Kuehl; P Leif Bergsagel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-10-01
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2013-02-01     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3456-63     Citation Subset:  AIM; IM    
Affiliation:
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Bone Remodeling
Cell Transformation, Neoplastic
Cyclin D1 / physiology
Disease Progression
Drug Resistance, Neoplasm / genetics
Genes, Retinoblastoma
Genes, bcl-1
Humans
Immunoglobulin Heavy Chains / genetics
Immunophenotyping
Models, Biological
Monoclonal Gammopathy of Undetermined Significance / etiology,  genetics*,  pathology
Multiple Myeloma / etiology,  genetics*,  pathology
Neoplasm Proteins / genetics,  physiology
Neoplastic Stem Cells / pathology
Oncogene Proteins, Fusion / genetics,  physiology
Osteoclasts / physiology
Precancerous Conditions / etiology,  genetics*,  pathology
Retinoblastoma Protein / physiology
Signal Transduction / genetics,  physiology
Stem Cell Niche
Translocation, Genetic
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
AG020686/AG/NIA NIH HHS; CA100707/CA/NCI NIH HHS; CA133966/CA/NCI NIH HHS; CA136671/CA/NCI NIH HHS; R01 AG020686/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/CCND1 protein, human; 0/Immunoglobulin Heavy Chains; 0/Neoplasm Proteins; 0/Oncogene Proteins, Fusion; 0/Retinoblastoma Protein; 136601-57-5/Cyclin D1
Comments/Corrections

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