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Hematopoietic differentiation is required for initiation of acute myeloid leukemia [ATAC-seq]

ABSTRACT: Leukemia initiating cells (LICs) of acute myeloid leukemia (AML) may arise from self-renewing hematopoietic stem cells (HSCs) and from committed progenitors. However, it remains unclear how leukemia-associated oncogenes instruct LIC formation from cells of different origins and if differentiation along the normal hematopoietic hierarchy is involved. Here, using murine models with the driver mutations MLL-AF9 or MOZ-TIF2, we found that regardless of the transformed cell types, myelomonocytic differentiation to the granulocyte macrophage progenitor (GMP) stage is critical for LIC generation. Blocking myeloid differentiation through disrupting the lineage-restricted transcription factor C/EBPa eliminates GMPs, blocks normal granulopoiesis, and prevents AML development. In contrast, restoring myeloid differentiation through inflammatory cytokines “rescues” AML transformation. Our findings identify myeloid differentiation as a critical step in LIC formation and AML development, thus guiding new therapeutic approaches.

ORGANISM(S): Mus musculus

PROVIDER: GSE71688 | GEO | 2015/08/04

SECONDARY ACCESSION(S): PRJNA291951

REPOSITORIES: GEO

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Hematopoietic differentiation is required for initiation of acute myeloid leukemia [ATAC-seq]

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