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Washington University in St. Louis
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Epigenetics, Hematology, Hematopoietic Stem Cell, Molecular Biology, Stem Cell Biology
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Dnmt3a Regulates Hematopoietic Stem Cells Via Dna Methylation-Independent Functions, Won Kyun Koh
Dnmt3a Regulates Hematopoietic Stem Cells Via Dna Methylation-Independent Functions, Won Kyun Koh
Arts & Sciences Electronic Theses and Dissertations
Hematopoiesis is strictly regulated to sustain blood production throughout adult life. De novo DNA methyltransferase 3-alpha (DNMT3A) is one of the major epigenetic regulators found to have an essential role in hematopoietic stem cell (HSC) differentiation. DNMT3A mutations are prevalent in myeloid diseases and malignancies that include acute myeloid leukemia (AML; ~22%), myelodysplastic syndrome (MDS; ~10%), and myeloproliferative neoplasm (MPN; ~8%). Importantly, DNMT3A mutations are not only the founding events of HSC malignant transformation, but they are also occurring as pre-leukemic lesions. Therefore, it is necessary to evaluate the molecular changes that occur in DNMT3A mutant HSCs, and how those …