github link
Accession IconGSE3725

MLL-AF9 transforms committed progenitors to leukemia stem cells by activation of a stem cell program

Organism Icon Mus musculus
Sample Icon 28 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Expression 430A Array (moe430a)

Submitter Supplied Information

Description
Leukemias and other cancers possess a rare population of cells capable of self-renewal, and eradication of these cancer stem cells is likely necessary for long-term cancer-free survival. Given that both normal and cancer stem cells are capable of self-renewal the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. We introduced the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23) found in human acute myelogenous leukemia (AML) into murine committed granulocyte-macrophage progenitors (GMP). The resultant leukemias contained cells with an immunophenotype similar to normal GMP that were highly enriched for leukemia stem cells (LSC). Detailed gene expression comparisons between normal hematopoietic stem cells (HSC), committed progenitors, and the LSC population demonstrated the LSC were globally more similar to the normal GMP than any other population. However, a subset of genes highly expressed in normal stem cells was re-activated in the LSC. These data demonstrate LSC can be generated from committed progenitors without widespread reprogramming of gene expression, and a leukemia self-renewal associated signature is activated in the process. Our findings define progression from normal hematopoietic progenitor to leukemia stem cell, and suggest that targeting a self-renewal program expressed in an abnormal context may be possible.
PubMed ID
Total Samples
28
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Processing Information
Additional Metadata
No rows found
Loading...