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Epigenetic basis of stem cell identity in normal and malignant hematop…

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  • 2015-12-18


[BK21 Plus Seminar]

▶Subject: Epigenetic basis of stem cell identity in normal and malignant hematopoietic development

▶Speaker: Namyoung Jung, Ph.D.(Johns Hopkins University School of Medicine)

▶Date: 2:00 PM/Jan. 7(Thur.)/2016

▶Place: Conference room(#179), Postech Biotech Center

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by subpopulations of leukemia-initiating or leukemia stem cells (LSC) that give rise to clonally related non-stem leukemic blasts. The LSC model proposes that since LSC and their blast progeny are clonally related, their functional properties must be due to epigenetic differences. In addition, the cell of origin of LSC among normal hematopoietic stem and progenitor cells (HSPCs) has yet to be clearly demonstrated. Here, we show an LSC DNA methylation signature, derived from xenograft and integration with gene expression that is comprised of 71 genes and identifies a key role for the HOXA cluster. Most of the genes are epigenetically regulated independently of underlying mutations, although several are downstream targets of epigenetic modifier genes mutated in AML. The LSC epigenetic signature is associated with poor prognosis independent of known risk factors such as age and cytogenetics. Furthermore, we characterized epigenetic changes during normal human hematopoietic development and identified key novel regulators for hematopoietic differentiation such as HMHB1 and MIR539. We found global hypomethylation as a critical mechanism of lineage commitment and variable epigenetic regulation in human hematopoiesis compared to murine hematopoiesis. The analysis of early hematopoietic progenitors from normal individuals reveals two distinct clusters of AML LSC resembling either lymphoid-primed multipotent progenitors (L-MPPs) or granulocyte/macrophage progenitors (GMPs). These results provide the first evidence for DNA methylation variation between AML LSCs and their blast progeny, and identify epigenetically distinct subgroups of AML likely reflecting the cell of origin.

▶Inquiry: Prof. Sung Ho Ryu (279-2292)
* This seminar will be given in English.
please refrain from taking photos during seminars. *

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