Abstract B12: Co-targeting of MYC and BCL2 signaling is a promising treatment strategy for double hit and triple hit B-cell lymphomas
| العنوان: | Abstract B12: Co-targeting of MYC and BCL2 signaling is a promising treatment strategy for double hit and triple hit B-cell lymphomas |
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| المؤلفون: | Sepehr Rokshar, Bekir Cinar, Serhan Alkan, Raju Pillai, Fred P. Rosenfelt, Melissa Cervania, Munevver Cinar, Jean Lopategui |
| المصدر: | Molecular Cancer Research. 13:B12-B12 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cancer Research, Vincristine, medicine.diagnostic_test, Cell growth, Biology, medicine.disease, BCL6, Lymphoma, Flow cytometry, medicine.anatomical_structure, Oncology, Apoptosis, hemic and lymphatic diseases, medicine, Cancer research, Doxorubicin, Molecular Biology, B cell, medicine.drug |
| الوصف: | Background: Overexpression of MYC and BCL2 or/and BCL6 due to genomic rearrangements is the key molecular feature of double hit lymphoma (DHL) or triple hit lymphoma (THL). Patients with DHL and THL show very aggressive disease course and poor survival because there is no effective treatment modality. The objective of this study is to assess the impact of MYC and BCL2 inhibition on established DHL and patient derived THL cells in vitro. Methods: Primary THL cell line named as CS-THL1 was established from an 85 year-old lymphoma patient. Immunohistochemistry (IHC) was conducted to determine the levels of MYC, BCL2, BCL6, or Ki-67 expression in formalin-fixed, paraffin-embedded tissues. MTS assays were employed to evaluate the anti-growth efficacy of MYC inhibitor 10058-F4 or JQ-1, and BCL-2 inhibitor ABT-199, a BH3 mimetic, in CS-THL1 and DoGKiT cells alone or together and with or without vincristine or doxorubicin. Apoptosis, cytochrome c release and intracellular expression of BCL2, BCL-xL, BIM, and MCL-1 protein in response to drugs were analyzed by flow cytometry. Results: Expression of MYC, BCL2, BCL6 and proliferation factor Ki-67 protein was increased in THL, as shown by IHC. Analysis of cell viability demonstrated that inhibition of MYC by 10058-F4 or JQ-1 or BCL2 by ABT-199 as a single agent significantly attenuated the growth of CS-THL1 and DoGKiT cells in dose- and time-dependent manners. Combination of 10058-F4 or JQ-1 and ABT-199 or together with vincristine or doxorubicin synergistically suppressed CS-THL1 and DoGKiT cell growth compared with single agent treatment. As demonstrated by multiple approaches, apoptosis due to inhibition of BCL2 by ABT-199 or inhibition of MYC with 10058-F4 or JQ-1 exposure was the underlying cause of the observed growth retardation in CS-THL1 and DoGKiT cells. Conclusion: These observations suggest that concurrent inhibition of MYC and BCL2 pathway signaling is a potential treatment modality for patients with aggressive DH and TH B-cell lymphomas. Citation Format: Munevver Cinar, Fred Rosenfelt, Sepehr Rokshar, Raju Pillai, Jean Lopategui, Melissa Cervania, Bekir Cinar, Serhan Alkan. Co-targeting of MYC and BCL2 signaling is a promising treatment strategy for double hit and triple hit B-cell lymphomas. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B12. |
| تدمد: | 1557-3125 1541-7786 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::4513c94d64aedbb024a008ec4a1d3916Test https://doi.org/10.1158/1557-3125.myc15-b12Test |
| رقم الانضمام: | edsair.doi...........4513c94d64aedbb024a008ec4a1d3916 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573125 15417786 |
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