Document Detail

Imatinib mesylate (STI571) inhibits multiple myeloma cell proliferation and potentiates the effect of common antimyeloma agents.
MedLine Citation:
PMID:  14632777     Owner:  NLM     Status:  MEDLINE    
c-Kit has been shown to be mutated in several types of tumours, and its activity has been correlated with increased proliferation rates in a subset of multiple myeloma (MM) patients. We have investigated the effect of imatinib mesylate (STI571), an inhibitor of c-Kit, on MM cells. STI571 inhibited the proliferation of MM cells by arresting cell cycle progression. Western blotting of cell cycle proteins showed that STI571 increased the levels of p21 and p16. MM cells expressed abl, but its level of tyrosine phosphorylation was low and unaffected by treatment with STI571. c-Kit was also expressed in certain MM cell lines, and its phosphorylation was stimulated by stem cell factor. However, the failure to detect the receptor protein in other MM cell lines in which cell proliferation was inhibited by STI571 suggests that its effect on these c-Kit-negative MM cell lines might be caused by the action of the drug on yet unknown targets. STI571 inhibited the proliferation of MM cells resistant to dexamethasone or melphalan and had an additive effect when combined with dexamethasone. Efforts to understand the action of STI571 in MM cells may help to identify these potentially useful targets in the treatment of this and other disorders.
Atanasio Pandiella; Xonia Carvajal-Vergara; Soraya Tabera; Gema Mateo; Norma Gutiérrez; Jesús F San Miguel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  123     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-24     Completed Date:  2004-01-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  858-68     Citation Subset:  IM    
Centro de Investigación del Cáncer, Instituto de Microbiología Bioquímica, and Hospital Universitario de Salamanca, Salamanca, Spain.
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Cell Cycle / drug effects
Cell Division / drug effects
Cell Line, Tumor
Dexamethasone / therapeutic use
Drug Synergism
Enzyme Activation
Flow Cytometry
Mitogen-Activated Protein Kinases / metabolism
Multiple Myeloma / drug therapy*,  metabolism,  pathology
Piperazines / therapeutic use*
Protein-Tyrosine Kinases / antagonists & inhibitors*
Pyrimidines / therapeutic use*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib; 50-02-2/Dexamethasone; EC Kinases; EC Protein Kinases

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