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Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells
- Source :
- Cell stem cell. 4(2)
- Publication Year :
- 2008
-
Abstract
- SummaryThe genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional subprogram more akin to that of embryonic stem cells (ESCs) than to that of adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3, and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when coexpressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia-initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor-prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells (CSCs) to prognosis in human cancer.
- Subjects :
- Oncogene Proteins, Fusion
Transcription, Genetic
Chromosomal Proteins, Non-Histone
CELLCYCLE
Biology
Article
Mice
Cancer stem cell
hemic and lymphatic diseases
HMGB3 Protein
medicine
Genetics
Animals
Humans
Progenitor cell
Cells, Cultured
Embryonic Stem Cells
Oligonucleotide Array Sequence Analysis
Gene Expression Regulation, Leukemic
Gene Expression Profiling
Gene Expression Regulation, Developmental
Myeloid leukemia
Histone-Lysine N-Methyltransferase
Cell Biology
Cellular Reprogramming
medicine.disease
STEMCELL
Embryonic stem cell
Oncogene Proteins v-myb
Mice, Inbred C57BL
Leukemia, Myeloid, Acute
Disease Models, Animal
Chromobox Protein Homolog 5
Cancer research
Neoplastic Stem Cells
Myeloid-Lymphoid Leukemia Protein
Molecular Medicine
Stem cell
Chronic myelogenous leukemia
Adult stem cell
Subjects
Details
- ISSN :
- 18759777
- Volume :
- 4
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cell stem cell
- Accession number :
- edsair.doi.dedup.....41e7c93c017135a568985dff9098d743