Myeloproliferative neoplasms are associated with increased risk for thrombotic complications. These conditions most commonly involve somatic mutations in genes that lead to constitutive activation of the Janus-associated kinase signaling pathway (eg, Janus kinase 2, calreticulin, myeloproliferative leukemia protein). Acquired gain-of-function mutations in these genes, particularly Janus kinase 2, can cause a spectrum of disorders, ranging from clonal hematopoiesis of indeterminate potential, a recently recognized age-related promoter of cardiovascular disease, to frank hematologic malignancy. Beyond thrombosis, patients with myeloproliferative neoplasms can develop other cardiovascular conditions, including heart failure and pulmonary hypertension. The authors review the pathophysiologic mechanisms of cardiovascular complications of myeloproliferative neoplasms, which involve inflammation, prothrombotic and profibrotic factors (including transforming growth factor-beta and lysyl oxidase), and abnormal function of circulating clones of mutated leukocytes and platelets from affected individuals. Anti-inflammatory therapies may provide cardiovascular benefit in patients with myeloproliferative neoplasms, a hypothesis that requires rigorous evaluation in clinical trials.
Keywords: ASXL1, additional sex Combs-like 1; CHIP, clonal hematopoiesis of indeterminate potential; DNMT3a, DNA methyltransferase 3 alpha; IL, interleukin; JAK, Janus-associated kinase; JAK2, Janus kinase 2; LOX, lysyl oxidase; MPL, myeloproliferative leukemia protein; MPN, myeloproliferative neoplasm; STAT, signal transducer and activator of transcription; TET2, tet methylcytosine dioxygenase 2; TGF, transforming growth factor; atherosclerosis; cardiovascular complications; clonal hematopoiesis; myeloproliferative neoplasms; thrombosis.
© 2022 The Authors.