Pluto Bioinformatics

GSE76748: The Histone Methyltransferases MLL1 and DOT1L Cooperate with Meningioma-1 to Induce AML [Mouse Dot1l ko RNA-seq]

Bulk RNA sequencing

Purpose: To characterize transcriptional changes associated with homozygous inactivation of Dot1l or Mll1 in MN1 driven AML; Methods: We sequenced mRNA from murine LSK-cells transformed using forced expression of MN1 (MSCV-MN1-IRES-GFP), and transduced with Cre-vector to inactivate either Dot1l or Mll1. Cells were sorted for Cre-expression (pTomato fluorescent marker) or expression of an inert control vector.; Results: Inactivation of either Dot1l or Mll1 in this model leads to a substantial delay or complete abrogation of leukemia development. Loss of Dot1l or Mll1 are associated with gene expression changes that have substantial overlap. In addition, genes that are downregulated follwing inactivation of Dot1l or Mll1 have substantial overlap with the gene set upregulated in MN1 transduced CMPs.; Conclusions: MN1 mediated leukemogenesis is associated with a gene expression program that dependes on Mll1 and Dot1l SOURCE: Tobias Neff (Tobias.Neff@ucdenver.edu) - Neff University of Colorado Denver AMC