New generation small-molecule inhibitors in myeloproliferative neoplasms.
OBJECTIVE
Myeloproliferative neoplasms (MPNs) are diseases that carry the JAK2 (V617F) mutation in about 70% of the patients. The purpose of this review is to describe the recent advances in the therapy of MPNs with JAK2 inhibitors.


RESULTS
Many drugs are now under investigations targeting different pathways critical for MPN development, such as the JAK-STAT (JAK2 inhibitors: INCB018424 or ruxolitinib, TG101348 or SAR302503, CYT387, SB1518, CEP701 and LY2784544) and the PI3K/AKT/mTOR (everolimus) pathways, or act through remodeling of chromatin with a key role in epigenetics (givinostat, panobinostat and vorinostat). The most relevant effects were spleen size reduction and relief of constitutional symptoms.


CONCLUSIONS
Patients who might benefit from JAK2 inhibitors in clinical practice are mostly those with splenomegaly or with constitutional symptoms. We should alert patients with lower hemoglobin levels that these therapies might, although temporarily, favor the need for red blood cell transfusions.
Division of Hematology, Department of Internal Medicine, Ospedale di Circolo e Fondazione Macchi, Varese, Italy. francesco.passamonti@ospedale.varese.it
Francesco
F
Passamonti
Margherita
M
Maffioli
Domenica
D
Caramazza
D000818:Animals; D001549:Benzamides / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D051379:Mice; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D009570:Nitriles; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D000096926:Benzenesulfonamides
D001549:Benzamides; D053614:Janus Kinase 2; D053612:Janus Kinases; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011759:Pyrrolidines; D013449:Sulfonamides; C528327:fedratinib; D000096926:Benzenesulfonamides; C546012:N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; C540383:ruxolitinib; C507924:JAK2 protein, human