Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD–positive leukemic cells
| العنوان: | Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD–positive leukemic cells |
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| المؤلفون: | Anne Marie O'Farrell, Kevin W.H. Yee, Julie M. Cherrington, Marcus M Schittenhelm, Troy Bainbridge, Laura McGreevey, Michael Heinrich, Ajia Town |
| المصدر: | Blood. 104:4202-4209 |
| بيانات النشر: | American Society of Hematology, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Indoles, Daunorubicin, medicine.drug_class, medicine.medical_treatment, Immunology, Antineoplastic Agents, Biology, Biochemistry, Antimetabolite, Cell Line, fluids and secretions, Cell Line, Tumor, hemic and lymphatic diseases, Sunitinib, medicine, Humans, Pyrroles, Chemotherapy, Leukemia, Cell growth, Cytarabine, Intracellular Signaling Peptides and Proteins, Drug Synergism, Zinc Fingers, hemic and immune systems, Cell Biology, Hematology, embryonic structures, Fms-Like Tyrosine Kinase 3, Cancer research, FLT3 Inhibitor, Cell Division, medicine.drug |
| الوصف: | Fetal liver tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutations are the most common molecular abnormality associated with adult acute myeloid leukemia (AML). To exploit this molecular target, a number of potent and specific FLT3 kinase inhibitors have been developed and are currently being tested in early phase clinical trials of patients with refractory AML. To explore the efficacy of combining a FLT3 inhibitor with standard AML chemotherapy drugs, we tested the effect of combining the FLT3 inhibitor SU11248 with cytarabine or daunorubicin on the proliferation and survival of cell lines expressing either mutant (FLT3 ITD or FLT3 D835V) or wild-type (WT) FLT3. SU11248 had additive-to-synergistic inhibitory effects on FLT3-dependent leukemic cell proliferation when combined with cytarabine or daunorubicin. The synergistic interaction of SU11248 and the traditional antileukemic agents was more pronounced for induction of apoptosis. SU11248 inhibited the proliferation of primary AML myeloblasts expressing mutant FLT3 ITD but not WT FLT3 protein. Combining SU11248 and cytarabine synergistically inhibited the proliferation of primary AML myeloblasts expressing FLT3 ITD but not WT FLT3 protein. These data suggest that the addition of potent FLT3 inhibitors such as SU11248 to AML chemotherapy regimens could result in improved treatment results. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09691d2ff7e2aed89127826f3d19d6a3 https://doi.org/10.1182/blood-2003-10-3381 |
| رقم الأكسشن: | edsair.doi.dedup.....09691d2ff7e2aed89127826f3d19d6a3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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