The t(11;19)(q23;p13.3) translocation leading to the expression of an MLL-ENL fusion is one of the most prevalent alterations affecting the mixed lineage leukemia 1 (MLL1) gene, mostly associated with B-cell acute lymphoblastic leukemia (ALL). Using a doxycycline (DOX)-inducible transgenic mouse model (iMLL-ENL) we show that direct induction or induction following transplantation of hematopoietic stem cells (HSC) but not of committed myeloid granulocyte-macrophage progenitors (GMP) leads to reversible acute mixed lineage leukemia. Disease induction was associated with iMLL-ENL levels exceeding the endogenous Mll1. iMLL-ENL leukemia was composed of small B220High cells with higher leukemia-initiating potential than co-existing larger-sized B220Low cells. Collectively, characterization of a novel transgenic mouse model indicates that the cell-of-origin and the expression levels above Mll1/MLL1 are both critical determinants for mixed lineage leukemia induced by the MLL-ENL fusion. SOURCE: Antoine Peters (antoine.peters@fmi.ch) -  Friedrich Miescher Institute for Biomedical Research (FMI)

Pluto Bioinformatics

GSE84988: Expression of MLL-ENL in hematopoietic stem cells induces mixed lineage acute leukemia