Cell Death Differ: MLKL-mediated G-CSF release promotes myeloid differentiation in acute myeloid leukemia

Acute myeloid leukemia (AML) is characterized by the accumulation of genetic aberrations in hematopoietic stem/progenitor cells
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Genetic aberrations usually inhibit the myeloid differentiation and cell death of cells, which are two key hallmarks of AML

Acute myeloid leukemia (AML) is characterized by the accumulation of genetic aberrations in hematopoietic stem/progenitor cells

The blockade of cell differentiation in AML, as a hallmark of AML, is largely due to the dysfunction of lineage-specific transcription factors that control cell differentiation
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The destruction of transcription factor function is mainly caused by chromosome translocation, gene mutation or transcription inhibition

In this study, the researchers found that MLKL (mixed lineage kinase domain-like protein) can promote the differentiation of hematopoietic progenitor cells transformed in AML
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Studies in mouse models of targeted genes have shown that MLKL can promote the release of G-CSF (granulocyte colony stimulating factor) by controlling the membrane permeabilization of leukemia cells

MLKL (mixed lineage kinase domain-like protein) can promote the differentiation of hematopoietic progenitor cells transformed in AML

MLKL expression is significantly reduced in AML patients

MLKL expression is significantly reduced in AML patients

Researchers found that Mlk1-/- hematopoietic stem cells and progenitor cells released less G-CSF, but at the same time retained the cells’ CSF3 (G-CSF) mRNA expression, G-CSF protein translation, and G-CSF receptor signal transduction.
Ability
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stem cell

The expression level of MLKL is related to the inflammatory response characteristics in AML

The expression level of MLKL is related to the inflammatory response characteristics in AML

Further studies have shown that MLKL is related to early endosomes and can regulate the release of G-CSF from the cell by mediating the formation of plasma membrane pores, while the absence of MLKL does not affect cell death
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It is worth noting that the expression level of MLKL is significantly reduced in AML patients, especially in patients with low-risk AML subtypes

The expression level of MLKL is significantly reduced in AML patients, especially in patients with low-risk AML subtypes

MLKL promotes cellular differentiation in myeloid leukemia by facilitating the release of G-CSF.

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