Hijack the HiJAKer: rethinking therapy for JAK2-mutant MPN

In this issue of Blood, Bonal et al 1 report on a mouse model of JAK2V617Fmutant myeloproliferative neoplasm (MPN) induced by low-level chimerism following bone marrow transplantation (BMT) of JAK2V617F cells into unconditioned homeostatic recipient mice.Using this approach that mimics somatically acquired clones in patients, the authors found that these JAK2V617F cells significantly affect both the recipient's BM microenvironment and unmutated nave hematopoiesis, thereby skewing the recipient's nonmutant hematopoietic system toward an MPN-like phenotype.These findings will have major implications for MPN therapy.