MPL-dependent and -independent features of JAK2V617F-driven MPN phenotypes. MPL plays a critical role in JAK2V617F MPNs by driving long-term self-renewal of HSCs, promoting megakaryocyte (MK) hyperplasia, thrombocytosis, and progression to MF. In contrast, other hallmark features of JAK2V617F MPNs such as erythrocytosis, leukocytosis, splenomegaly, and the production of proinflammatory cytokines that contribute to spleen fibrosis occur independently of MPL signaling. Figure created with Biorender.com.