Transcriptomics

Dataset Information

8

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


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. Primary KSL, CMP, and GMP cells from wildtype controls and C/Ebpa knockouts were used for RNA extraction and hybridization on Affymetrix microarrays. We also compared the microarray samples of leukemic granulocyte macrophage progenitor compartments (L-GMPs) from MLL-AF9 transformed control or cytokine rescued C/EBPa KO leukemic mouse bone marrow and their secondary recipients with those non-Leukemia KSLs and CMPs from MLL-AF9 transduecd KO recipients with no leukemia development.

ORGANISM(S): Mus musculus  

SUBMITTER: Christinan Bach   Min Ye  Robert S Welner  Daniel G Tenen  Junyan Zhang  Elena Levantini  Scott Armstrong  Hong Zhang  Richard Koche  Philipp Staber  Henry Yang 

PROVIDER: E-GEOD-71687 | ArrayExpress | 2015-08-04

SECONDARY ACCESSION(S): GSE71687PRJNA291952

REPOSITORIES: GEO, ArrayExpress

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