Article
5-Azacytidine supports the long-term repopulating activity of cord blood CD34(+) cells.
Fujisaki Cell Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
American Journal of Hematology (impact factor:
4.67).
12/2004;
77(3):313-5.
DOI:10.1002/ajh.20178
pp.313-5
Source: PubMed
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Citations (0)
- Cited In (2)
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Article: Epigenetic "bivalently marked" process of cancer stem cell-driven tumorigenesis.
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ABSTRACT: Silencing of tumor suppressor genes (TSGs), by DNA methylation, is well known in adult cancers. However, based on the "stem cell" theory of tumorigenesis, the early epigenetic events arising in malignant precursors remain unknown. A recent report demonstrates that, while pluripotent embryonic stem cells lack DNA methylation and possess a "bivalent" pattern of activating and repressive histone marks in numerous TSGs, analogous multipotent malignant cells derived from germ cell tumors (embryonic carcinoma cells) gain additional silencing modifications to those same genes. These results suggest a possible mechanism by which aberrant differentiation, mediated by histone and DNA methylation, instigates tumor progression.BioEssays 10/2007; 29(9):842-5. · 4.95 Impact Factor -
Article: CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors.
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ABSTRACT: The DNA hypomethylating drug decitabine maintains normal hematopoietic stem cell (HSC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. The basis for these contrasting cell fates, and for selective CpG hypomethylation by decitabine, is poorly understood. Promoter CpGs, with methylation measured by microarray, were classified by the direction of methylation change with normal myeloid maturation. In AML cells, the methylation pattern at maturation-responsive CpGs suggested at least partial maturation. Consistent with partial maturation, in gene expression analyses, AML cells expressed high levels of the key lineage-specifying factor CEBPA, but relatively low levels of the key late-differentiation driver CEBPE. In methylation analysis by mass spectrometry, CEBPE promoter CpGs that are usually hypomethylated during granulocyte maturation were significantly hypermethylated in AML cells. Decitabine-induced hypomethylation was greatest at these and other promoter CpGs that are usually hypomethylated with myeloid maturation, accompanied by cellular differentiation of AML cells. In contrast, decitabine-treated normal HSCs retained immature morphology, and methylation significantly decreased at CpGs that are less methylated in immature cells. High expression of lineage-specifying factor and aberrant epigenetic repression of some key late-differentiation driver genes distinguishes AML cells from normal HSCs, and could explain the contrasting differentiation and methylation responses to decitabine.Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2011; 26(2):244-54. · 8.30 Impact Factor
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Keywords
5-AzaC treatment
biological phenomena
colony-forming activity
correlations
demethylating reagent
differentiation system
DNA methylation
embryonic development
hematopoietic progenitor cells
human umbilical cord blood
long-term culture-initiating
LTC-IC
LTC-IC frequency 1.57-
nontreated control
normal hematopoietic differentiation
regulating
wide range