〔Abstract〕 Objective To explore the role ofPtpn11 E76 K /+;Mx1-Cre+activating mutant bone marrow-derived exosomes in the occurrence of myeloproliferative neoplasma(MPN). Methods Ptpn11 E76 K /+;Mx1-Cre+activating mutant bone marrow-derived exosomes were co-cultured with normal hematopoietic stem cellsin vitro, and at the same time, mutant exosomes were injected into normal mice through the tail vein to observe the effects of exosomesin vivo. The mouse cytokine array panel was used to detect the specific changes in the exosomes derived from the mutant bone marrow. Results Exosomes derived from mutant bone marrow could carry series of inflammatory factors, which accelerated the myeloid differentiation of normal hematopoietic stem cells, leading to the occurrence of MPN in normal mice. After inhibiting inflammatory factors, the symptoms of MPN in mice were relieved, and the expression of inflammatory factors in exosomes also decreased. Conclusion Ptpn11 E76 K /+;Mx1-Cre+activating mutant bone marrow-derived exosomes can trigger MPN in miceviainflammatory factors. Both exosomes and the inflammatory factors they carry can be potential targets for MPN therapy.