Epigenetics in AML – DNA hypermethylation within the DNMT3A gene in AML patients

DNA-methylation (DNAm) of CpG dinucleotides is a key epigenetic process. Upon cell division, the DNAm pattern is maintained on the newly synthesized DNA strand by DNA methyltransferase 1 (DNMT1), whereas DNAm pattern changes are triggered by DNMT3A and DNMT3B that act as de novo methyltransferases.
DNMT3A and DNMT3B play a pivotal role in the epigenetic regulation and development of hematopoietic malignant myeloid disease, such as acute myeloid leukemia (AML) and myelodysplastic syndrome. About 22% of AML patients harbor mutations in DNMT3A, which likely cause the disease. However, little is known about how DNMT3s are epigenetically controlled.
The present invention provides a novel diagnostic and prognostic method for hematopoietic malignant myeloid disease. This method is based on the identification of aberrant hypermethylation at an internal promoter region of DNMT3A, which occurs in about 40% of AML patients.

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