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

Notes: NA Not applicable