Table 8.

Summary of potential novel therapies available for ETP-ALL.

Type of Novel Therapy	Rationale	Therapeutic Target	Single Treatment or Proposed Combined Treatment	Data from Pre-clinical Studies for ETP-ALL Available?	Data from Clinical Studies for ETP-ALL Patients Available (Except Case Reports)?
JAK inhibitor (ruxolitinib)	JAK/STAT pathway hyperactivation is common in ETP-ALL	JAK	Single treatment	Yes	No
Anti-CD33 (gemtuzumab)	CD33 expression is frequently present in ETP-ALL	CD33	Single treatment	Yes	No
Anti-CD38 (daratumumab)	CD38 expression is frequently present in ETP-ALL	CD38	1. Single treatment 2. Combined with nelarabine	Yes	No
Anti-CD123	CD123 expression is prevalent in ETP-ALL	CD123	Single treatment	No	No
CAR-T	Genetically engineered patient’s T cells to target against various antigens present on ETP-ALL	CD5, CD7	Single treatment	Yes	No
Hypomethylating agents (decitabine, azacytidine)	1. DNA hypermethylation associated with PRC2 mutations2. High rate of DNMT2A mutation in adult ETP-ALL	1. Targeting epigenetic regulation of gene transcriptions2. Upregulation of NOXA in AML	Combination therapy with venetoclax or combined chemotherapy	No	No
BCL-2 inhibitor (venetoclax)	ETP-ALL is highly dependent on BCL-2 activity	BCL-2	1. Single treatment 2. Combination therapy with conventional chemotherapy, hypomethylating agents, bortezomib, navitoclax	Yes	Yes
FLT3 inhibitors	FLT3-ITD and FLT3-TKD mutations are common in ETP-ALL	FLT3	Single treatment	No	No
BET inhibitors	Frequent PRC2 mutations in ETP-ALL	BET protein	Single treatment	Yes	No