Novel strategies for patients with chronic myeloproliferative disorders.
OBJECTIVE
This review focuses on new strategies for unmet clinical needs and on new targeted therapies in classical Philadelphia-negative myeloproliferative neoplasms.


RESULTS
Meta-analyses in essential thrombocythemia documented Janus kinase 2 (JAK2) V617F as being associated with increased risk of thrombosis. New studies reinforced the evidence of leukocytosis as an independent risk factor for thrombosis in polycythemia vera and essential thrombocythemia. In a phase II trial of pegylated interferon-alpha2a in polycythemia vera patients, a decrease of JAK2 mutant expression to undetectable levels was demonstrated. New trials documented that 5-azacytidine and bortezomib have negligible effect in primary myelofibrosis, whereas thalidomide and tipifarnib produce 22 and 44% response, respectively. In primary myelofibrosis, the JAK2 inhibitor, INCB018424, resulted in a rapid and marked reduction in splenomegaly and a clinical improvement, with a modest effect on JAK2 V617F burden.


CONCLUSIONS
Treating low-risk essential thrombocythemia and polycythemia vera patients presenting with leukocytosis or JAK2 V617F mutation in order to prevent thrombosis deserves a prospective validation. Pursuing clonal remission in polycythemia vera by interferon needs new evidence. Tipifarnib may be added to conventional therapeutic instruments for symptomatic primary myelofibrosis. The results of anti-JAK2-targeted therapies are encouraging as regards symptoms reduction but not clonal remission.
Barosi
Giovanni
G
Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, Pavia, Italy. barosig@smatteo.pv.it
Rosti
Vittorio
V
D002908:Chronic Disease; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics*; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines; D015363:Quinolones / Q000627:therapeutic use; D011994:Recombinant Proteins; D013792:Thalidomide / Q000627:therapeutic use
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; D015363:Quinolones; D011994:Recombinant Proteins; D013792:Thalidomide; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C402769:tipifarnib