JAK2 V617F: implications for thrombosis in myeloproliferative diseases.
OBJECTIVE
A major cause of morbidity in myeloproliferative disorders is thrombosis, although the pathophysiology of this process remains poorly understood. The review will explore the relationship between thrombosis and the recently identified gain-of-function mutation in Janus kinase 2, found in the majority of patients with myeloproliferative disorders.


RESULTS
In 2005, several groups described an acquired point mutation in the pseudokinase domain of Janus kinase 2 (JAK2 V617F). Subsequently, interest has focused on the utility of JAK2 V617F as both a diagnostic and prognostic tool, and as a potential therapeutic target. Retrospective data have identified JAK2 V617F as a risk factor for thrombosis in essential thrombocythemia, and have also shown a tight association between JAK2 V617F and abdominal vein thrombosis.


CONCLUSIONS
A general theme is that JAK2 V617F is variably associated with thrombosis and, more consistently, associated with elevations in blood counts relative to mutation-negative myeloproliferative disorders; future preclinical research should focus on the pathophysiology of thrombosis in myeloproliferative disorders, particularly in terms of the relationship between dysregulated Janus kinase 2 and elevated blood counts. A better understanding of this causal pathway will inform clinical studies, lead to improved risk stratification and, ideally, a reduction in thrombotic episodes.
Hexner
Elizabeth O
EO
Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. elizabeth.hexner@uphs.upenn.edu
D019943:Amino Acid Substitution; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D018570:Risk Assessment; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000628:therapy; D013927:Thrombosis / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000628:therapy
C507924:JAK2 protein, human; D053614:Janus Kinase 2