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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-12-16
pubmed:abstractText
Chronic myeloid leukemia (CML) is a clonal stem cell disorder that is characterized by the acquired chromosomal translocation BCR-ABL. This gives rise to a constitutively active tyrosine kinase deregulation of the normal mechanisms of cell cycle control. In the normal hematopoietic system, hematopoietic stem cells (HSC) self-renew to form identical daughter cells but also differentiate to mature blood cells. Leukemic stem cells (LSC) share these properties of self-renewal and also differentiate to mature leukemic cells. LSC have been isolated from patients with CML: these cells give rise to leukemia following transplantation into NOD-SCID mice models. Further characterization of CML stem cells has demonstrated that a small percentage of these cells are quiescent despite culture with growth factors. The CML stem cell arises from a normal HSC that has acquired the Philadelphia chromosome. In advanced phase, more mature cells such as granulocyte/monocyte progenitors might also acquire the ability to self-renew and function as LSC. This might be one of the mechanisms underlying the progression to blast crisis. Quiescent stem cells are resistant to treatment with imatinib in vitro and are thought also to show resistance in vivo. The properties of the stem cells that lead to this drug resistance are still being characterized. However, this drug insensitivity leads to disease persistence that may lead to disease relapse even despite an initial response to imatinib. Newer molecular therapies are in development that act to specifically target and eradicate the stem cell pool.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:issn
1938-0712
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9 Suppl 4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S376-81
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The chronic myeloid leukemia stem cell.
pubmed:affiliation
The Beatson West of Scotland Cancer Centre, Glasgow, UK. emma.nicholson@nhs.net
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't