No evidence of frequent association of the JAK2 V617F mutation with acute myocardial infarction in young patients

Myeloproliferative neoplasms (MPNs) have been associated with high incidence of thrombosis and bleeding episodes, which significantly contribute to disease-related morbidity and mortality.1 Notably, clinical data indicate an association of the JAK2 V617F mutation, seen in nearly all polycythemia vera cases and half of those with essential thrombocythemia with erythrocytosis, leukocytosis and thrombotic complications. Particularly for essential thrombocythemia, a recent overview has suggested that the JAK2 V617F positivity may be associated with an increased risk of thrombosis, an effect mediated by the leukocytosis conferred by the mutation.2 Several studies have indicated that a substantial proportion of patients with idiopathic Budd–Chiari syndrome, portal vein or mesenteric vein thrombosis carry the JAK2 V617F mutation, even in the absence of overt clinical or hematological features of an MPN.3 Detection of JAK2 V617F mutation in this setting is a marker of a ‘latent’ MPN as positive patients appear to have bone marrow histological features characteristic of MPN.3, 4

Recently, Mercier et al. screened 27 patients aged <40 years, who had experienced an acute myocardial infarction (AMI). Three out of 27 (11.1%) patients carried the JAK2 V617F mutation, leading the authors to conclude that a latent MPN may often be present in this group of patients, warranting screening for the V617F mutation.5 In contrast, in a study of 28 patients with AMI at a young age (defined as <50 years), none was found to harbour the JAK2 V617F mutation. That group of patients was part of a larger cohort of patients with arterial or venous thrombosis outside the splanchnic circulation. The study suggested that screening for JAK2 V617F mutation is not warranted as part of the hypercoagulable work-up in patients with non-splanchnic thrombosis.6

We investigated the prevalence of the JAK2 V617F mutation in a prospectively assembled cohort of AMI patients aged <35 years. We hypothesized that JAK2 V617F may be further enriched in this group of patients as it represents a good model because the mainly genetic factors, and to a lesser extent the environmental factors, have an impact on the pathogenesis of the thrombosis. We studied consecutive patients admitted to our institution between January 1998 and December 2005 who had suffered their first AMI under the age of 35 years. DNA was extracted from peripheral blood samples by standard procedures after isolation of total leukocytes following red-cell lysis. The JAK2 V617F mutation was detected using a tetra-primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) assay with a sensitivity of 1%.7 The observed incidence of JAK2 V617F mutated cases was compared with the incidence of 5% using the Clopper–Pearson exact test. Statistical analysis was performed using STATA, version SE/10 (STATA Corp, College Station, TX). Significance was defined as P-value <0.05; P-values were two-tailed.8 The study was approved by the internal review boards from all the participating institutes and written informed consent was obtained from all patients according to the Declaration of Helsinki.

We enrolled 147 patients (125 male and 22 female) with no evidence of an underlying MPN who had suffered an AMI under the age of 35 years. Detailed clinical information was available for 135 (92%) cases: the mean age was 32 years (s.d., 3 years), all were on standard post-AMI treatment (β-blockers, angiotensin-converting enzyme inhibitors, antiplatelets and statins) and 30 (22.2%) suffered a second acute coronary event during follow-up. The JAK2 V617F mutation was not detected in any case, yielding a 95% confidence interval for the prevalence of the mutation ranging from 0 to 2.48% and excluding a 5% prevalence of JAK2 V617F in this population (P=0.001). On the basis of this large cohort of young patients with AMI, our findings indicate that a latent JAK2 V617F-positive MPN is an unlikely cause of coronary arterial thrombosis that leads to AMI, although we cannot exclude the possibility of a small, significant excess of JAK2 V617F over background levels. Thus, our findings reinforce the suggestion that screening for the JAK2 V617F mutation may not be warranted for all patients with unexplained thrombosis and should probably be restricted to those who present with splanchnic venous thrombosis and those with non-splanchnic thrombosis associated with clinical or laboratory findings suggestive of an MPN diagnosis.6, 9, 10


  1. 1

    Elliott MA, Tefferi A . Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128: 275–290.

  2. 2

    Dahabreh IJ, Zoi K, Giannouli S, Zoi C, Loukopoulos D, Voulgarelis M . Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical outcomes in essential thrombocythemia. Leuk Res 2009; 33: 67–73.

  3. 3

    Boissinot M, Lippert E, Girodon F, Dobo I, Fouassier M, Masliah C et al. Latent myeloproliferative disorder revealed by the JAK2-V617F mutation and endogenous megakaryocytic colonies in patients with splanchnic vein thrombosis. Blood 2006; 108: 3223–3224.

  4. 4

    Kiladjian JJ, Cervantes F, Leebeek FW, Marzac C, Cassinat B, Chevret S et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood 2008; 111: 4922–4929.

  5. 5

    Mercier E, Cochery-Nouvellon E, Lavigne G, Bertinchant JP, Gris JC . In support of the revised World Health Organization diagnostic criteria for essential thrombocythemia: JAK2 V617F and premature myocardial infarction. J Thromb Haemost 2008; 6: 206–207.

  6. 6

    Pardanani A, Lasho TL, Hussein K, Schwager SM, Finke CM, Pruthi RK et al. JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients. Mayo Clin Proc 2008; 83: 457–459.

  7. 7

    Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005; 106: 2162–2168.

  8. 8

    Newcombe RG . Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med 1998; 17: 857–872.

  9. 9

    Remacha AF, Estivill C, Sarda MP, Mateo J, Souto JC, Canals C et al. The V617F mutation of JAK2 is very uncommon in patients with thrombosis. Haematologica 2007; 92: 285–286.

  10. 10

    Pardanani A, Lasho TL, Schwager S, Finke C, Hussein K, Pruthi RK et al. JAK2V617F prevalence and allele burden in non-splanchnic venous thrombosis in the absence of overt myeloproliferative disorder. Leukemia 2007; 21: 1828–1829.

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This work was supported by the grant PENED03ED934/2003 to DL from the Secretariat for Research and Technology of the Greek Ministry of Development.

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Politou, M., Zoi, C., Dahabreh, I. et al. No evidence of frequent association of the JAK2 V617F mutation with acute myocardial infarction in young patients. Leukemia 23, 1008–1009 (2009).

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