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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-4
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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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABT-737,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Harringtonines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/homoharringtonine
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1365-2141
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pubmed:author |
pubmed-author:AndreeffMichaelM,
pubmed-author:AshiharaEishiE,
pubmed-author:KamitsujiYuriY,
pubmed-author:KawataEriE,
pubmed-author:KimuraShinyaS,
pubmed-author:KurodaJunyaJ,
pubmed-author:MaekawaTairaT,
pubmed-author:MatsumotoYosukeY,
pubmed-author:MurotaniYoshihideY,
pubmed-author:StrasserAndreasA,
pubmed-author:TakeuchiMikiM,
pubmed-author:TanakaHideoH,
pubmed-author:TanakaRurikoR,
pubmed-author:TaniwakiMasafumiM,
pubmed-author:YokotaAsumiA
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pubmed:issnType |
Electronic
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pubmed:volume |
140
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
181-90
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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
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pubmed:year |
2008
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pubmed:articleTitle |
ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms.
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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
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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