JAK2 mutation and thrombosis in the myeloproliferative neoplasms.
The clinical course of the classic myeloproliferative neoplasms (MPNs) is burdened by an increased rate of cardiovascular events, which are the major cause of mortality. Age and history of thrombosis are the criteria used to stratify patients to the most appropriate therapeutic options. However, the mechanisms ultimately responsible for the increased thrombotic tendency have not yet been elucidated; abnormalities of blood cell count, neutrophil and platelet activation, and a state of hypercoagulability can all occur. Recurrent mutations in JAK2 or MPL have been described in MPNs and serve as disease markers. There is also evidence that a JAK2V617F mutant state represents an independent factor associated with thrombosis, and abnormalities of cell function attributable to JAK2V617F have been characterized. It is hoped that elucidation of the role mutant JAK2 plays in MPNs will improve our understanding of the pathophysiology of thrombosis and eventually result in improved patient treatment using molecularly targeted drugs.
Vannucchi
Alessandro M
AM
Unità Funzionale di Ematologia, Università degli Studi, Florence, Italy. amvannucchi@unifi.it
D019943:Amino Acid Substitution; D001241:Aspirin / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics* / Q000502:physiology; D015337:Multicenter Studies as Topic; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000097:blood / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D011799:Quinazolines / Q000627:therapeutic use; D019851:Thrombophilia / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control
D005343:Fibrinolytic Agents; D016898:Interferon-alpha; D011799:Quinazolines; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C021139:anagrelide; D001241:Aspirin