Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-4
pubmed:abstractText
The effect of ABT-737, a BH3-mimicking inhibitor for anti-apoptotic Bcl-2 and Bcl-X(L), but not Mcl-1, against Bcr-Abl-positive (Bcr-Abl(+)) leukaemic cells was examined. ABT-737 potently induced apoptosis in Bcr-Abl(+) chronic myeloid leukaemia (CML) cell lines and primary CML samples in vitro and prolonged the survival of mice xenografted with BV173 cells, a CML cell line. Higher expression of anti-apoptotic Bcl-2 proteins reduced cell killing by ABT-737 in each cell line, but there was no correlation between the sensitivities to ABT-737 and the specific expression patterns of Bcl-2 family proteins among cell lines. Thus, the cell killing effect of ABT-737 must be determined not only by the expression patterns of Bcl-2 family proteins but also by other mechanisms, such as high expression of Bcr-Abl, or a drug-efflux pump, in CML cells. ABT-737 augmented the cell killing effect of imatinib in Bcr-Abl(+) cells with diverse drug-resistance mechanisms unless leukaemic cells harboured imatinib-insensitive Abl kinase domain mutations, such as T315I. The combination of homoharringtonine that reduces Mcl-1 enhanced the killing by ABT-737 strongly in Bcr-Abl(+) cells even with T315I mutation. These results suggest that ABT-737 is a useful component of chemotherapies for CML with diverse drug-resistance mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1365-2141
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-90
pubmed:meshHeading
pubmed-meshheading:18028486-Animals, pubmed-meshheading:18028486-Antineoplastic Agents, pubmed-meshheading:18028486-Antineoplastic Agents, Phytogenic, pubmed-meshheading:18028486-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:18028486-Apoptosis, pubmed-meshheading:18028486-Biphenyl Compounds, pubmed-meshheading:18028486-Dose-Response Relationship, Drug, pubmed-meshheading:18028486-Drug Evaluation, Preclinical, pubmed-meshheading:18028486-Drug Resistance, Neoplasm, pubmed-meshheading:18028486-Harringtonines, pubmed-meshheading:18028486-Humans, pubmed-meshheading:18028486-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:18028486-Male, pubmed-meshheading:18028486-Mice, pubmed-meshheading:18028486-Mice, Inbred NOD, pubmed-meshheading:18028486-Mice, SCID, pubmed-meshheading:18028486-Neoplasm Transplantation, pubmed-meshheading:18028486-Nitrophenols, pubmed-meshheading:18028486-Piperazines, pubmed-meshheading:18028486-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:18028486-Sulfonamides, pubmed-meshheading:18028486-Survival Analysis, pubmed-meshheading:18028486-Transplantation, Heterologous, pubmed-meshheading:18028486-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms.
pubmed:affiliation
Division of Haematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan. junkuro@koto.kpu-m.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural