TABLE 5.

Current precision medicine approaches to target JAK2 in JAK2-altered ALL and their associated benefits and disadvantages.

Therapeutic strategy	Examples	Benefits	Disadvantages
Type-I inhibitors	Ruxolitinib	May reduce blast counts when in combination with chemotherapy	Withdrawal syndrome
	Fedratinib		Resistant/persistent disease
	Momelotinib		Cytopenia
	Pacritinib
Type-II inhibitors	BBT594	High JAK2 specificity	Risk of severe cytopenia
	CHZ868	May not associate with withdrawal syndrome	Risk of resistant/persistent disease
			Development of both available inhibitors has terminated
Allosteric inhibitors (type-III inhibitors)	LS104	Lower risk of cytopenia	Binding mechanisms of available inhibitors unknown
	ON044580	May be less susceptible to resistant/persistent disease	Development of both available inhibitors has terminated
			Association with withdrawal syndrome unknown
HSP90 inhibitors	PU-H71	May reduce blast counts when in combination with type-I JAK inhibitors	Associated with severe adverse events
	AUY922	Degrades JAK2 harboring inhibitor-resistant mutations	Unknown risk of resistant disease
		Not associated with withdrawal syndrome	Development of both available inhibitors has terminated
HDAC inhibitors	Panobinostat	May reduce blast counts when in combination with type-I JAK inhibitors	May associate with severe adverse events
	Vorinostat	Degrades JAK2 harboring inhibitor-resistant mutations	Unknown risk of resistant disease
	Givinostat	Not associated with withdrawal syndrome
PROTACS	-	Demonstrates superior efficacy than ruxolitinib in vivo	Risk of cytopenia and adverse events
		Should degrade JAK2 harboring inhibitor-resistant mutations	Unknown risk of resistant disease
		Not associated with withdrawal syndrome