Document Detail


Chronic myeloid leukemia blast crisis arises from progenitors.
MedLine Citation:
PMID:  17218393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic myeloid leukemia (CML) progresses through three distinct clinical stages: chronic phase, accelerated phase, and blast crisis. The progression to accelerated phase and blast crisis is driven by activation of oncogenes, inactivation of tumor suppressor genes, and/or amplification of the BCR-ABL fusion gene, which causes the chronic phase of the disease. The cell of origin of blast crisis is a subject of speculation. Here, I develop a simple mathematical model of CML blast crisis to investigate whether blasts arise from leukemic stem cells or more differentiated leukemic cells. I use data of patients treated with imatinib and previous agents to estimate the effects of therapy on the rate of progression. Imatinib reduces the progression rate 10-fold as compared with previous (ineffective) therapies. If blasts were produced by leukemic stem cells, there would be no difference in the rate of progression between patients treated with imatinib and previous therapies, because imatinib seems to be incapable of depleting leukemic stem cells. Imatinib does, however, deplete leukemic progenitors. Therefore, CML blasts are likely to arise from leukemic progenitors. Disclosure of potential conflicts of interest is found at the end of this article.
Authors:
Franziska Michor
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Publication Detail:
Type:  Journal Article     Date:  2007-01-11
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  25     ISSN:  1066-5099     ISO Abbreviation:  Stem Cells     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-05-01     Completed Date:  2007-05-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1114-8     Citation Subset:  IM    
Affiliation:
Harvard University, Society of Fellows, 78 Mt Auburn Street, Cambridge, Massachusetts 02138, USA. michor@fas.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Blast Crisis / drug therapy,  pathology*
Disease Progression
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy,  pathology*
Models, Immunological
Mutation
Neoplastic Stem Cells / pathology*
Piperazines / therapeutic use
Pyrimidines / therapeutic use
Chemical
Reg. No./Substance:
0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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