Arachidonic acid promotes myeloid differentiation of splenic CD45- Ter119+ cells in myeloproliferative neoplasm.

Although splenic CD45^-Ter119⁺ cells promote cancer progression by secreting artemin, it remains unclear whether these cells play an important role in myeloproliferative neoplasm (MPN). Here, using a Kras^G12D/+-induced mouse model of MPN, we demonstrated that the number and cycling of CD45^-Ter119⁺ cells increased in the spleens of MPN mice. Moreover, these cells could differentiate into myeloid cells upon stimulation with GM-CSF and mIL-6. Through RNA sequencing, we further revealed that myeloid genes, such as Hoxa9, Mpo and Ms4a3, were highly expressed in CD45^-Ter119⁺ cells. Mechanistically, we showed that the arachidonic acid content was significantly elevated in splenic CD45^-Ter119⁺ cells, and exogenous arachidonic acid mediated the differentiation of splenic CD45^-Ter119⁺ cells into myeloid cells. Our results revealed that splenic CD45^-Ter119⁺ cells play a crucial role in myeloid leukemia and that arachidonic acid could be a potential therapeutic target for MPN treatment.