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Table 2 Summary of combination studies using BET inhibitors in hematologic malignancies

From: Super-enhancers: critical roles and therapeutic targets in hematologic malignancies

Disease Combination Effect Reference
Lymphoma OTX015, mTOR inhibitor everolimus, BTK inhibitors ibrutinib, HDAC inhibitor vorinostat, and anti-CD20 monoclonal antibody rituximab Synergic anti-lymphoma activity in vitro and in vivo Boi M, et al [154]; Gaudio E, et al [155].
Diffuse large B cell lymphoma cell lines and xenograft mouse model
Activated B-cell-like (ABC) DLBCL cells and xenograft mouse model JQ1, BTK kinase inhibitor rbrutinib Reduce IκB kinase activity and inhibit cells proliferation Ceribelli M, et al [151]
Lymphoma-derived cell lines BAY 1238097, EZH2 inhibitor DZNep, GSK-126, everolimus and ibrutinib Synergistic cytotoxicity in vitro Bernasconi E, et al [156]
B- cell lymphoma xenograft mouse model RVX2135, ATR inhibitor AZ20 Enhanced sensitivity to ATR inhibitor in vitro and in mouse models of B-cell lymphoma, and improve survival Muralidharan, et al.
Myc-transgenic mice lymphoma models RVX2135, HDAC inhibitor panobinostat, vorinostat Inhibit proliferation and induce apoptosis of lymphoma cells Bhadury, et al [141]
Human lymphoma B-cell lines JQ1, rituximab JQ1 Increase Rituximab sensitivity in lymphoma cells with CYCLON and MYC expression Emadali A, et al [152]
Primary effusion lymphoma (PEL) cell lines and orthotopic xenograft model JQ1, lenalidomide Synergistic cytotoxicity in PEL cell lines an increased the survival of PEL bearing NOD–SCID mice Gopalakrishnan, et al [157]
Mantle cell lymphoma cell lines and mice models CPI203, lenalidomide Synergistic antitumor activity in bortezomib-resistant mantle cell lymphoma Moros A, et al [153]
Leukemia JQ1, cytarabine (ARA-C) Synergistic anti-leukemic effects Herrmann H, et al [146]
Acute myeloid leukemia (AML) cell lines HL60 and KG1
Patient-derived AML cells and mice model JQ1, JAKi ruxolitinib, HSP90i AUY922 Inhibit growth and induce apoptosis of patient-derived AML cells, and improved survival of mice engrafted with AML cells; Enhanced sensitivity to ruxolitinib-resistant AML cells. Saenz DT, et al [158]
 AML cell lines, primary patient samples, and xenograft models BI 894999, CDK9 Inhibitors flavopiridol, LDC000067 Synergistic antitumor effects and lead to rapid induction of apoptosis in vitro and in vivo. Gerlach D, et al [101]
AML cells expressing FLT3-ITD and TKI-resistant cell lines JQ1, FLT3 inhibitor ponatinib, AC220, panobinostat Inhibit growth and induce apoptosis of human AML cells; Synergistic induction of apoptosis in TKI-resistant cells Fiskus W, et al [140]
AML xenograft mouse model ABBV-075, Bcl-2 inhibitor venetoclax, hypomethylating agent azacitadine, proteasome inhibitor bortezomib augments the activities of venetoclax, azacitidine, in xenograft models of AML. Bui MH, et al [144]
Human AML xenograft models INCB054329 and LSD1 Inhibitor INCB059872 Enhanced myeloid differentiation and apoptosis in human AML cell lines Liu X, et al [145]
Human T-cell acute lymphoblastic leukemia (T-ALL) cells JQ1 and CK2 inhibitor CX-4945 Induce apoptosis in human T-ALL cells, Lian H, et al [149]
Primary Acute lymphoblastic leukaemia (ALL) cases, ALL cell lines and ALL xenograft models JQ1 and dexamethasone JQ1 sensitized ALL cells to dexamethasone, and reduced subcutaneous tumor growth in ALL xenograft models. Da Costa D, et al [147]
Myeloma INCB054329 and JAK inhibitors (ruxolitinib or itacitinib) Inhibit myeloma cell growth in vitro and in vivo Stubbs MC, et al [102]
 Multiple myeloma (MM) models
In vitro and in vivo models of MM CPI203 and lenalidomide/dexamethasone Improve therapy response in relapsed/refractory patients with MM Díaz T, et al [159]
bortezomib and melphalan resistant MM cell lines and patients sample CPI203 and bortezomib enhanced apoptosis and anti-proliferative effects Siegel M B, et al [160]
  1. Compounds in boldface are BET inhibitors