Roles of megakaryocytes and platelets in myeloproliferative neoplasms

PURPOSE OF REVIEW: The purpose of this review is to describe the activity and function megakaryocytes and platelets in the myeloproliferative neoplasms (MPNs.) Specific attention is paid to how megakaryocytes relate to disease progression and altered hemostasis and how current therapies are beginning to target them. RECENT FINDINGS: MPN megakaryocytes are hyperproliferative and induce further dysregulation within the niche via inflammatory cytokine secretion, while MPN platelets display a contradictory phenotype of baseline preactivation and functional exhaustion upon stimulation, due in part to mitochondrial dysregulation. Platelet transcriptomic profiling has further revealed disease subtype-specific gene expression and a shared thrombo-inflammatory profile. CALR-mutated MPNs have significantly advanced with the development of mutation-specific interventions in early clinical trials. SUMMARY: Thrombotic and hemorrhagic complications represent the most common cause of morbidity in MPNs, however the mechanisms underlying this pathology remain opaque. Cytoreduction and antithrombotic therapies, the mainstay for treatment of MPNs, inadequately address platelet dysfunction, though emerging therapies targeting the MPN clone are promising. Thus, a deeper understanding of megakaryocyte and platelet biology in MPNs is essential for the development of precise therapeutic strategies to reduce thrombotic complications and improve patient outcomes.