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Here we report about the preclinical activity of GS, a novel BET inhibitor, in CLL. IκBα modulation indicates that GS also inhibited NF-κB signaling. GSinduced apoptosis resulted from an imbalance between positive BIM and negative regulators BCL-X L of the intrinsic apoptosis pathway.

The antileukemia activity of GS increased synergistically in combinations with B-cell receptor signaling inhibitors, the BTK inhibitor ibrutinib, the PI3Kδ inhibitor idelalisib, and the SYK inhibitor entospletinib. In cocultures that mimic the lymph node microenvironment, GS inhibited signaling pathways within nurselike cells and their growth, indicating that BET inhibitors also can target the supportive CLL microenvironment.

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The antileukemia activity of GS increased synergistically in combinations with B-cell receptor signaling inhibitors, the BTK inhibitor ibrutinib, the PI3Kδ inhibitor idelalisib, and the SYK inhibitor entospletinib. In cocultures that mimic the lymph node microenvironment, GS inhibited signaling pathways within nurselike cells and their growth, indicating that BET inhibitors also can target the supportive CLL microenvironment.

Collectively, these data provide a rationale for the clinical evaluation of BET inhibitors in CLL. Contact Us. Meet the News Team. Advertise with Us. Submit Photo or Video. Jobs with Gray Television.

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