Clonal Hematopoiesis and Atherosclerosis

Abstract

Jaiswal and colleagues (July 13 issue)¹ report that the presence of clonal hematopoiesis of indeterminate potential (CHIP) was associated with coronary heart disease. However, the use of the JAK2 V617F mutation as a marker of CHIP may be misleading, particularly when the mutant allele burden is high (up to 52% in this study). Unlike all the other mutations that were evaluated by the authors, JAK2 V617F is an initiating mutation that causes deregulated production of red cells and platelets.² It is a major criterion in the classification of the World Health Organization (WHO) for a diagnosis of myeloproliferative neoplasms, diseases that are often diagnosed after major thrombosis, including myocardial infarctions.^3-5 Jaiswal and colleagues considered that leukocyte counts can be used to rule out myeloproliferative neoplasms, whereas hematocrit and platelet counts are much more relevant for this purpose, especially in polycythemia vera and essential thrombocythemia. In the absence of full blood counts, one could speculate that many of the patients with a high JAK2 V617F allele burden are more likely to have undiagnosed myeloproliferative neoplasms than to be healthy CHIP carriers. Therefore, we suggest that the JAK2 V617F mutation should not be included in the definition of CHIP because of its specific involvement in the pathogenesis of myeloproliferative neoplasms.