Evi1 governs Kdm6b-mediated histone demethylation to finely regulate the Laptm4b-driven mTORC pathway in vivo [LSK]
Ecotropic viral integration site 1 (EVI1/MECOM) overexpression is common in myeloid malignancies. We present a new Evi1 transgenic mouse model with inducible expression in hematopoietic stem cells (HSCs) and progenitor cells (HPCs) at lower levels. Upon exogenous Evi1 induction, mice displayed anemia, thrombocytopenia, lymphopenia, and dysplasia in erythroid and megakaryocyte cells with a significant expansion of committed myeloid progenitor cells, resembling human Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN)-like disease. Methods: LSK cells were sorted by Sony SH800 from 3  pairs of mice transplanted with WT BM cells and Evi1-OE BM cells after pIpC injection. Around 5X103 LSK cells were harvested from each mouse. Then the cells were lysated by Trizol and total RNA was extracted by phenol-chloroform. Results: Molecular pathways altered in LSK cells from recipient mice transplanted with Evi1-OE BM cells. Conclusions: Transcription profile changed in Evi1 overexpressing hematopoietic stem and progenitor cells. Overall design: 3  pairs of recipient mice transplanted with WT or Evi1-OE BM cells were sacrificed after pIpC injection to induce Evi1 overexpression. And the BM cells were harvested. LSK cells were sorted.