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

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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.

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