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Role of DNA Methyltransferases and DNA Methylation in Cell Fate Decisions During Blood Cell Development and Leukemia

  • Grant A. Challen
  • Jennifer J. Trowbridge
Chapter
Part of the Epigenetics and Human Health book series (EHH)

Abstract

Increasing evidence indicates that DNA methylation and the proteins responsible for catalyzing DNA methylation (the DNA methyltransferases or DNMTs) play critical roles in embryonic specification of the blood cell lineage and during differentiation of adult hematopoietic stem cells (HSCs). Furthermore, the identification of somatic mutations in DNMTs in a high frequency of human blood cancers suggests that altered DNA methylation is a critical component of leukemogenesis. This review will highlight our current understanding of the function of DNA methylation and the major DNMTs in hematopoiesis, describe the extent of characterization of mutant DNMTs in human blood cancer and other diseases, and discuss strategies to target altered DNA methylation or the activity of mutant DNMTs for more precise and effective leukemia therapy. Future studies aimed at understanding how DNA methylation regulates gene expression in concert with other epigenetic modifications, how DNMTs are directed to their cell type-specific target loci, and the exact biological functions of mutant DNMTs will be pivotal in the development of novel, targeted therapies for blood cancers.

Keywords

DNA methylation DNMT Epigenetics Hematopoiesis Leukemia 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Division of Oncology, Department of Internal MedicineWashington University in St. LouisSt. LouisUSA
  2. 2.The Jackson LaboratoryBar HarborUSA

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