New insights into the pathogenesis and treatment of chronic myeloproliferative disorders.
OBJECTIVE
The classic BCR-ABL negative myeloproliferative disorders are at a crossroads of rapidly evolving pathogenetic understanding, leading to changes in diagnostic criteria and potentially targeted therapy. This review focuses on the implications of these changes relative to current standards.


RESULTS
The V617F activating mutation of Janus kinase 2, and associated parallel mutations, is at least partially responsible for myeloproliferation (and potentially vascular events) associated with myeloproliferative disorders. It is unclear whether the mutation facilitates progression to the blast phases of myeloproliferative disorders.


CONCLUSIONS
The high prevalence of the V617F mutation of Janus kinase 2 and associated mutations in myeloproliferative disorders (> 95% in polycythemia vera and about half of patients with essential thrombocythemia and primary myelofibrosis) has led the World Health Organization to alter the diagnostic criteria for these myeloproliferative disorders, and these changes are reviewed. Current therapy for myeloproliferative disorders remains largely based on preventing vascular events and symptomatic control, with allogeneic stem cell transplantation for high-risk patients. Investigational approaches to myeloproliferative disorders involve targeting the bone marrow microenvironment and DNA hypermethylation. Phase I clinical testing of inhibition of Janus kinase 2, active in vitro, began with several agents in 2007; the results are highly anticipated.
Mesa
Ruben A
RA
Division of Hematology, Mayo Clinic College of Medicine, 200 First St. S.W., Rochester, Minnesota 55905, USA. mesa.ruben@mayo.edu
D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000503:physiopathology / Q000628:therapy
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D053614:Janus Kinase 2