JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative Neoplasms

Table 1

Current therapies for BCR-ABL1 negative MPN patients to be combined with JAK2 inhibitors.

Drug	Target	Results	JAK2V617F load	Reference
JAK2 inhibitors
INCB018424; Ruxolitinib	JAK2, JAK1	>50% reduction in splenomegaly and constitutional symptoms	JAK2V617F load marginally reduced	Verstovsek et al. [29]
TG101348 or; SAR302503	JAK2, FLT3	Reduction in splenomegaly	JAK2V617F load significantly reduced	Pardanani et al. [34]
CYT387	JAK2, JAK1, TYK2	In a murine model, normalized erythrocytes, leukocytes, spleen size, and levels of inflammatory cytokines	JAK2V617F load reduced	Tyner et al. [35]
CEP-701; Lestaurtinib	JAK2, FLT3	Reduction in splenomegaly	JAK2V617F load no reduced	Hexner et al. [36]; Santos et al. [37]
Immunomodulators
Interferon-alpha	Stromal cells	Inhibit cytokine signalling, proliferation and angiogenesis	Unknown	Kiladjian et al. [43]
Thalidomide	Stromal cells	Inhibition of angiogenesis	Unknown	Jabbour et al. [45]
Lenalidomide	Stromal cells	Inhibition of angiogenesis	Unknown	Jabbour et al. [45]
Pomalidomide	Stromal cells	Inhibition of angiogenesis	Unknown	Begna et al. [46]
Other
Hydroxycarbamide	JAK2 mutant burden	Inhibition of proliferation	JAK2V617F load significantly reduced	Besses et al. [47]
Histone; post-translationa; modificators	JAK2 nuclear	Depletion of JAK2V617F autophosphorylation, apoptosis in vitro	Unknown	Wang et al. [26]