In MF, MPN disease-propagating stem cells aberrantly mobilize from the bone marrow to the spleen. Several independent sources of data, including the current study, indicate that JAK2-mutant MPN stem cells are not effectively targeted by JAK inhibition. The current study by Wang et al suggests that following treatment with a JAK inhibitor, MPN progenitor cells in the spleens of patients with MF undergo apoptosis resulting in a reduction in splenomegaly. JAK inhibitor clinical trial data indicate that circulating proinflammatory cytokine levels decrease following JAK inhibition. Whether suppressing the inflammatory milieu through JAK inhibition could potentially delay progression or even reverse MF within the bone marrow, without selectively targeting the malignant hematopoietic clone, remains to be determined.