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| Status |
Public on Mar 31, 2006 |
| Title |
Comparative analysis of BCR-ABL tyrosine kinase inhibitors in BCR-ABL positive K562 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Tyrosine kinase activity is the crucial enzymatic activity driving all known functions of the BCR-ABL protein and is required for protection from apoptosis by BCR-ABL, therefore, targeting this enzyme is an effective approach for therapeutic strategies. Recently, a novel structural entity, imatinib (STI571; Novartis, Basel, Switzerland), a potent and selective inhibitor of the tyrosine kinase activity of BCR-ABL, has shown promise against Ph-positive leukemia in human clinical trials. However, the emergence of imatinib resistance in patients with acute forms of Ph-positive leukemia has highlighted the need for overriding chemotherapy to eradicate this disease.
AMN107 and BMS-354825 are clinically active “next-generation” BCR-ABL inhibitors.
One potentially powerful approach is to use these compounds in combination with imatinib.
The rationale for such approaches is that an inhibitor cocktail may target the widest range of resistant clones and thereby delay the onset of acquired drug resistance. More potent BCR-ABL inhibitors would be to target residual leukemia that persists in patients in whom imatinib induces durable remission but failed to eradicate the disease. From these points, our studies are performed to determine
(1) the differences of molecular signaling pathways between BMS-354825 and imatinib
(2) the mechanisms by which drug resistance of BMS-354825 and imatinib occur except for point mutation of BCR-ABL kinase domain.
Keywords: drug sensitivity
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| Overall design |
(1)Comparison of gene expression patterens in K562 cells treated with tyrosine kinase inhibitors. For dual color analysis, K562 (MOC) was utilized as a reference.(i.e., Imatinib treated K562 cells vs BMS -354825 treated K562 cells vs Imatinib + BMS treated K562 cells).
(2) Compatrison of gene expression patterens between parental K562 cells and those in drug-resistant clones (i.e., K562-IMR and K562-BMSR).
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| Contributor(s) |
Ohyashiki JH, Tauchi T, Nunoda K, Ohyashiki K |
| Citation(s) |
17213809 |
| Submission date |
Jun 14, 2005 |
| Last update date |
Mar 16, 2012 |
| Contact name |
Junko H Ohyashiki |
| E-mail(s) |
junko@hh.iij4u.or.jp
|
| Phone |
+81-3-3342-6111(ext.5999)
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| Fax |
+81-3-5381-6651
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| Organization name |
Tokyo Medical University
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| Department |
Intractable Immune System Diseases Research Center
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| Street address |
6-7-1, Nishishinjuku, Shinjuku-ku
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| City |
Tokyo |
| ZIP/Postal code |
160-0023 |
| Country |
Japan |
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| Platforms (1) |
| GPL2531 |
Novusgene type 3 Hematology/Oncology TMU 667 array |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA92407 |
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