Determination of Driver Mutations in JAK2, MPL, and Calreticulin in Coronary Patients with Suspected Essential Thrombocythemia

Patients with essential thrombocythemia (ET) are at increased risk towards atherothrombotic complications. The JAK2 V617F mutation is found in at least half of the patients with ET and screening for JAK2 V617F mutational status has been included in the World Health Organization diagnostic criteria for ET. Further somatic driver mutations including mutations in exon 12 of the JAK2 gene, MPL mutations W515L/W515K, as well as mutations in exon 9 of the calreticulin (CALR) gene have been suggested as diagnostic markers for ET. Due to the close relation of ET to thrombotic events, early diagnosis of ET is of high clinical relevance, especially in patients with increased cardiovascular risk, like coronary patients. However, elevated blood cell counts are often ascribed to a reactive genesis within an acute coronary event. For this reason mostly no further clarification concerning myeloproliferative neoplasms is done.

In the present study, therefore, we determined the prevalence of JAK2 V617F, JAK2 exon 12, MPL W515L, MPL W515K, and CALR exon 9 mutations in a cohort of patients undergoing coronary angiography for the evaluation of suspected or established stable coronary artery disease and suspected diagnosis of ET. We aimed at identifying those with occult ET proposing need for additional treatment.

From a total of 1,589 coronary patients, 12 patients had increased platelets (>450 x10 ⁹/L) predisposing them to ET. Mutation analysis among these patients showed three individuals with the JAK2 V617F mutation and one with an ins/del mutation in exon 9 of the CALR gene confirming suspected diagnosis of ET. Consequently, frequency of ET was 0.25% among our coronary patients. For comparison, in the United States between 38 and 57 ET cases per 100,000 age-adjusted inhabitants have been reported. This corresponds to an up to 7-fold accumulation of ET cases in coronary patients compared to the general population.

We conclude that the prevalence of ET is increased in coronary patients compared to the general population. For this reason comprehensive mutation analysis should be considered in all cardiovascular risk patients with persistent elevation of thrombocytes, not only to identify patient subgroups at high risk but also to individualize therapeutic strategies.