Table 4 Mechanisms of HDACis combined with other agents in treating malignant hematopoiesis at preclinical settings
HDACis | Combination(s) | Cancer(s) | Mechanism(s) |
|---|---|---|---|
Vorinostat (SAHA) | Bortezomib | Relapsed/refractory MM | Increasing p21 and cleaved PARP expression |
|  | T-ALL | Inhibiting NF-κB signaling | |
Carfilzomib or Bortezomib | Relapsed/refractory B cell lymphomas | Decreasing NF-κB activation and increasing Bim levels | |
Rituximab | Lymphoma/leukemia | Increasing in p21 and acetylation of histone H3 leading to cell cycle arrest | |
ABT-737 | DLBCL | Inhibiting binding of BH3-only modulators and proapoptotic activators | |
MG-132 | Imatinib-resistant CML | Increasing intracellular ROS and repressing BCR-ABL expression | |
S116836 | Imatinib-resistant CML | Repressing antiapoptosis proteins Mcl-1 and XIAP, promoting Bim expression and mitochondrial damage | |
BI2536 | Imatinib-resistant CML | Triggering pronounced mitochondrial dysfunction, generating reactive oxygen species (ROS) and DNA damage | |
KW-2449 | Imatinib-resistant CML / AML | Inhibiting Bcr/Abl and inducing ROS and DNA damage | |
ABT-737 | Emu-myc lymphomas | Repressing BCR-ABL expression | |
Idarubicin + Cytarabine | Advanced AML or Aza–resistant MDS | Generating reactive oxygen species (ROS) | |
Panobinostat (LBH589) | Bortezomib | Relapsed/refractory TCL | Increasing acetylation of HSP90, downregulating mitogen-activated protein kinase pathway signaling |
Carfilzomib | Relapsed/refractory MM | Inhibiting p97, HDAC or PI3Kα | |
Ibrutinib | Relapsed/refractory MM | Generating ROS and inactivating ERK1/2 | |
ABT-199 | Ibrutinib-resistant CLL | Reducing BTK/mutated BTK protein and signaling | |
Ponatinib or Imatinib | AML | Upregulating Bim expression | |
Everolimus | Imatinib-resistant CML | Forcing histone acetylation and decreasing BCR-ABL and AKT signaling | |
Everolimus | HL/NHL | Activating the caspase pathway, inhibiting STAT5 and STAT6 phosphorylation, GLUT1 and mTOR | |
Romidepsin | Rituximab | Rituximab-resistant BL | Decreasing phosphorylated STAT3 binding to the MyD88 promotor |
ExPBNK | BL | Reducing p38 MAPK phosphorylation and enhancing MICA/B expression | |
Ara-C | AML | Enriching Myc- and HOXA9-regulated gene pathways and inducing cell cycle arrest and DNA damage | |
ATRA | APL | Inducing p21-mediated cell-cycle arrest and the expression of MDR1 | |
Gemcitabine, cisplatin and dexamethasone | DLBCL | Reducing LMP1 and c-myc expression | |
Belinostat | Vincristine or Paclitaxel | DLBCL | Inducing mitosis arrest and apoptosis |
Bortezomib | AML / ALL | Inhibiting NF-κB signaling and upregulating Bim expression | |
Entinostat | Sorafenib | Refractory/relapsed AML | Inhibiting HOXA9, MEIS1 and FLT3 |
KW-2449 | Imatinib-resistant CML / AML | Inhibiting Bcr/Abl, inducing ROS and DNA damage | |
Valproic acid | Decitabine | AML or MDS I/II | Inducing cell cycle arrest, DNA damage and apoptosis |
TRAIL/Apo2L | TRAIL/Apo2L-resistant CML | Increasing DR4 and DR5 expression | |
ABT-737 | Emu-myc lymphomas | Restricting Bcl-2 and Bcl-XL | |
Chloroquine (CQ) | AML | Inducing RASSF1A expression and inhibiting autophagy | |
MGCD0103 | Cytarabine or daunorubicin | AML | Inducing DNA damage and apoptosis |
Brentuximab vedotin | Relapsed/refractory HL | N/A | |
Azacitidine | High-risk MDS or AML | Increasing p15 and caspase-3 expression | |
AR-42 | Decitabine | M5 subtype-AML | Elevating miR-199b expression |
Lenalidomide | Lenalidomide-resistant MM | Upregulating miR-9-5p, downregulating IGF2BP3 and CD44 | |
Depsipeptide | ATRA | APL | Upregulating of MDR1 and inducing p21-mediated cell cycle arrest |
SBHA | ABT-737 | Relapsed/refractory MM | Upregulating Bim expression and disabling cytoprotective autophagy |
JSL-1 | Imatinib | Imatinib-resistant CML | Inhibiting γ-catenin |
Sodium phenylbutyrate | Azacitidine | AML or MDS | Reducing endoplasmic reticulum (ER) stress and ablating CHOP protein |