Of note, our AML model revealed that expression of MLL-ENL only had very limited impact on the transcriptome as well as open chromatin status of the Hoxb8-FL cells as long as they were cultured in multipotent, self-renewal conditions (ME-Parental cells), reminiscent of a previous report suggesting that highly purified HSCs are intrinsically protected against MLL-ENL-mediated transformation9. Here, HOXB8 is linked to acute myeloid leukemia.