biostudies-literatureWang XEuropean Research Council3235-3250https://www.ebi.ac.uk/biostudies/studies/S-EPMC8630008biostudies-literatureUnknown28(12)The blockade of cellular differentiation represents a hallmark of acute myeloid leukemia (AML), which is largely attributed to the dysfunction of lineage-specific transcription factors controlling cellular differentiation. However, alternative mechanisms of cellular differentiation programs in AML remain largely unexplored. Here we report that mixed lineage kinase domain-like protein (MLKL) contributes to the cellular differentiation of transformed hematopoietic progenitor cells in AML. Using gene-targeted mice, we show that MLKL facilitates the release of granulocyte colony-stimulating factor (G-CSF) by controlling membrane permeabilization in leukemic cells. Mlkl^-/- hematopoietic stem and progenitor cells released reduced amounts of G-CSF while retaining their capacity for CSFCell death and differentiationMLKL promotes cellular differentiation in myeloid leukemia by facilitating the release of G-CSF.PMC8630008682473Keller ECShi RMishra RHerold TShen BAgrawal DBassermann FJost PJGarcia-Saez AJDill VBelka CWang XSlotta-Huspenina JRos UfalseMLKL promotes cellular differentiation in myeloid leukemia by facilitating the release of G-CSF.The blockade of cellular differentiation represents a hallmark of acute myeloid leukemia (AML), which is largely attributed to the dysfunction of lineage-specific transcription factors controlling cellular differentiation. However, alternative mechanisms of cellular differentiation programs in AML remain largely unexplored. Here we report that mixed lineage kinase domain-like protein (MLKL) contributes to the cellular differentiation of transformed hematopoietic progenitor cells in AML. Using gene-targeted mice, we show that MLKL facilitates the release of granulocyte colony-stimulating factor (G-CSF) by controlling membrane permeabilization in leukemic cells. Mlkl^-/- hematopoietic stem and progenitor cells released reduced amounts of G-CSF while retaining their capacity for CSF2021-01-01T00:00:00Z2021 Dec2026-05-08T05:28:45.57Z2022-02-11T13:43:52.616ZS-EPMC86300083407907810.1038/s41418-021-00811-1