Linked Life Data

11986238

Source:http://linkedlifedata.com/resource/pubmed/id/11986238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-5-2
pubmed:abstractText
Imatinib mesylate (STI571) is a promising new treatment for chronic myelogenous leukemia (CML). The effect of imatinib mesylate on primitive malignant progenitors in CML has not been evaluated, and it is not clear whether suppression of progenitor growth represents inhibition of increased proliferation, induction of apoptosis, or both. We demonstrated here that in vitro exposure to concentrations of imatinib mesylate usually achieved in patients (1-2 microM) for 96 hours inhibited BCR/ABL-positive primitive progenitors (6-week long-term culture-initiating cells [LTCICs]) as well as committed progenitors (colony-forming cells [CFCs]). No suppression of normal LTCICs and significantly less suppression of normal CFCs were observed. A higher concentration of imatinib mesylate (5 microM) did not significantly increase suppression of CML or normal LTCICs but did increase suppression of CML CFCs, and to a lesser extent, normal CFCs. Analysis of cell division using the fluorescent dye carboxyfluorescein diacetate succinimidyl ester indicated that imatinib mesylate (1-2 microM) inhibits cycling of CML primitive (CD34(+)CD38(-)) and committed (CD34(+)CD38(+)) progenitors to a much greater extent than normal cells. Conversely, treatment with 1 to 2 microM imatinib mesylate did not significantly increase the percentage of cells undergoing apoptosis. Although a higher concentration of imatinib mesylate (5 microM) led to an increase in apoptosis of CML cells, apoptosis also increased in normal samples. In summary, at clinically relevant concentrations, imatinib mesylate selectively suppresses CML primitive progenitors by reversing abnormally increased proliferation but does not significantly increase apoptosis. These results suggest that inhibition of Bcr-Abl tyrosine kinase by imatinib mesylate restores normal hematopoiesis by removing the proliferative advantage of CML progenitors but that elimination of all CML progenitors may not occur.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3792-800
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11986238-Adolescent, pubmed-meshheading:11986238-Adult, pubmed-meshheading:11986238-Aged, pubmed-meshheading:11986238-Antineoplastic Agents, pubmed-meshheading:11986238-Apoptosis, pubmed-meshheading:11986238-Cell Division, pubmed-meshheading:11986238-Cells, Cultured, pubmed-meshheading:11986238-Dose-Response Relationship, Drug, pubmed-meshheading:11986238-Enzyme Inhibitors, pubmed-meshheading:11986238-Female, pubmed-meshheading:11986238-Fusion Proteins, bcr-abl, pubmed-meshheading:11986238-Humans, pubmed-meshheading:11986238-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:11986238-Male, pubmed-meshheading:11986238-Middle Aged, pubmed-meshheading:11986238-Myeloid Progenitor Cells, pubmed-meshheading:11986238-Piperazines, pubmed-meshheading:11986238-Pyrimidines
pubmed:year
2002
pubmed:articleTitle
Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation.
pubmed:affiliation
Division of Hematology and Bone Marrow Transplantation and the Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA 91010, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't