Linked Life Data

21250825

Source:http://linkedlifedata.com/resource/pubmed/id/21250825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2011-2-8
pubmed:abstractText
Imatinib mesylate (IM) has become standard therapy for patients with chronic myeloid leukemia (CML), but CML stem cells are intrinsically resistant to IM and to second/third-generation tyrosine kinase inhibitors (TKIs), allowing the persistence of a 'reservoir' of BCR-ABL-expressing CML-initiating cells potentially responsible for disease progression. Although it is still controversial whether the 'insensitivity' of CML stem cells to treatment with TKIs is due to BCR-ABL-dependent or independent mechanisms, recent evidence indicates that treatment with IM suppresses BCR-ABL-dependent signaling in CML stem cells with no adverse effects on their survival. Treatment of CML cells with IM/TKIs induces autophagy, a genetically regulated process of adaptation to metabolic stress which may allow tumor cells to become metabolically inert, enabling their survival under conditions that may mimic growth factor/nutrient deprivation. Based on this hypothesis, TKI-induced autophagy may 'antagonize' TKI-induced cell death and inhibition of autophagy may eliminate this survival mechanism by restoring 'sensitivity' of CML stem cells to treatment with IM/TKIs. Consistent with this, recent evidence indicates that phenotypically and functionally defined CML-enriched stem cells that are insensitive to treatment with TKIs are efficiently eliminated by the combination of TKI and chloroquine, an inhibitor of late stage autophagy. Thus, inhibition of autophagy may 'sensitize' CML stem cells to treatment with TKIs, thus preserving the high specificity of TKI-based therapies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1029-2403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
52 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-9
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Inhibition of autophagy: a new strategy to enhance sensitivity of chronic myeloid leukemia stem cells to tyrosine kinase inhibitors.
pubmed:affiliation
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. B_Calabretta@mail.jci.tju.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural