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Leuk Lymphoma. 2015 Jul;56(7):2146-52. doi: 10.3109/10428194.2014.981172. Epub 2015 Jan 28.

ABT-199, a BH3 mimetic that specifically targets Bcl-2, enhances the antitumor activity of chemotherapy, bortezomib and JQ1 in "double hit" lymphoma cells.

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1
Rutgers Cancer Institute of New Jersey and the Robert Wood Johnson School of Medicine , New Brunswick, NJ , USA.

Abstract

Double hit lymphoma (DHL) is a recently recognized lymphoma with a survival of less than 2 years. Both ABT-737, a Bcl-2/Bcl-XL inhibitor, and ABT-199, which selectively targets Bcl-2, were potently cytotoxic against DHL cell lines Sc-1 and OcI-LY18, the RL cell line and primary human DHL cells, but not Ramos cells, which lack Bcl-2 expression. ABT-199 was more potent than ABT-737, and is the most promising of the BH3 mimetics to date. The DHL cell lines were also sensitive (< 200 nM) to doxorubicin, methotrexate, cytarabine and the proteosome inhibitor, bortezomib. The combination of chemotherapy with ABT-199 and doxorubicin or cytarabine, bortezomib, YM-155 and JQ1 produced synergistic cell kill against the DHL cell lines. Cells from a patient with DHL were also sensitive to JQ1 and bortezomib, providing a rationale for a clinical trial of these combinations in patients with relapsed DHL.

KEYWORDS:

Cell lines and animal models; chemotherapeutic approaches; lymphoma and Hodgkin disease

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PMID:
25373508
DOI:
10.3109/10428194.2014.981172
[Indexed for MEDLINE]

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