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Life Sciences

Washington University in St. Louis

Theses/Dissertations

2016

Cancer

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The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole May 2016

The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole

Arts & Sciences Electronic Theses and Dissertations

Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and the highly homologous gene DNMT3B encode the two methyltransferases that are primarily responsible for mediating de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are mutually exclusive of several translocations that create oncogenic fusion genes (PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X), suggesting that these fusions may require functional DNMT3A to initiate leukemogenesis. Using bone marrow cells from a constitutive Dnmt3a null mouse, we show that loss of Dnmt3a caused a striking loss of DNA methylation throughout the genome of …