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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. Examination of chromatin accessibility in Cebpa knock-out and control conditions.

ORGANISM(S): Mus musculus

SUBMITTER: Richard Koche

PROVIDER: E-GEOD-71688 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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2015-08-04 | E-GEOD-71687 | biostudies-arrayexpress

Hematopoietic cell differentiation is required for initiation of acute myeloid leukemia

2014-09-17 | E-GEOD-61468 | biostudies-arrayexpress

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

2015-08-04 | GSE71688 | GEO

Hematopoietic cell differentiation is required for initiation of acute myeloid leukemia [Microarray expression]

2015-08-04 | GSE71687 | GEO

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