دورية أكاديمية
HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia
| العنوان: | HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia |
|---|---|
| المؤلفون: | Katja Seipel, Scarlett Kohler, Ulrike Bacher, Thomas Pabst |
| المصدر: | Current Issues in Molecular Biology, Vol 45, Iss 9, Pp 7011-7026 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | acute myeloid leukemia (AML), B-cell lymphoma 2 (BCL2), cell surface glycoprotein CD34, stem cell factor receptor c-KIT (CD117), heat-shock protein 90 (HSP90), fms-like tyrosine kinase 3 (FLT3), Biology (General), QH301-705.5 |
| الوصف: | Targeting the molecular chaperone HSP90 and the anti-apoptotic proteins MCL1 and BCL2 may be a promising novel approach in the treatment of acute myeloid leukemia (AML). The HSP90 inhibitor PU-H71, MCL1 inhibitor S63845, and BCL2 inhibitor venetoclax were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells. AML cells represented all major morphologic and molecular subtypes including FLT3-ITD and TP53 mutant AML cell lines and a variety of patient-derived AML cells. Results: PU-H71 and combination treatments with MCL1 inhibitor S63845 or BCL2 inhibitor venetoclax induced cell cycle arrest and apoptosis in susceptible AML cell lines and primary AML. The majority of the primary AML samples were responsive to PU-H71 in combination with BH3 mimetics. Elevated susceptibility to PU-H71 and S63845 was associated with FLT3 mutated AML with CD34 < 20%. Elevated susceptibility to PU-H71 and venetoclax was associated with primary AML with CD117 > 80% and CD11b < 45%. The combination of HSP90 inhibitor PU-H71 and MCL1 inhibitor S63845 may be a candidate treatment for FLT3-mutated AML with moderate CD34 positivity while the combination of HSP90 inhibitor PU-H71 and BCL2 inhibitor venetoclax may be more effective in the treatment of primitive AML with high CD117 and low CD11b positivity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1467-3045 1467-3037 |
| العلاقة: | https://www.mdpi.com/1467-3045/45/9/443Test; https://doaj.org/toc/1467-3037Test; https://doaj.org/toc/1467-3045Test |
| DOI: | 10.3390/cimb45090443 |
| الوصول الحر: | https://doaj.org/article/e9fd06a271dc4970ac830749cb3a1183Test |
| رقم الانضمام: | edsdoj.9fd06a271dc4970ac830749cb3a1183 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14673045 14673037 |
|---|---|
| DOI: | 10.3390/cimb45090443 |