Epigenetic therapy in allogeneic hematopoietic stem cell transplantation

DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG) islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decit...

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Bibliographic Details
Published in:Revista brasileira de hematologia e hemoterapia 2013, Vol.35 (2), p.126-133
Main Authors: Bashir, Qaiser, William, Basem Magdy, Garcia-Manero, Guillermo, de Lima, Marcos
Format: Article
Language:English
Subjects:
Azacitidine
DNA methyltransferase
Epigenesis, genetic
HEMATOLOGY
Hematopoietic stem cell transplantation
Immunologic factors
Leukemia, myeloid
MEDICINE, RESEARCH & EXPERIMENTAL
Review
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Summary:DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG) islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decitabine have anti-tumor activity against a broad range of malignancies, but have been investigated mostly in myelodysplastic syndrome. In addition, these agents have immunomodulatory effects that are under investigation in the allogeneic stem cell transplantation scenario. Both drugs have been used in the perioperative period of allogeneic transplantations with varying degrees of success. It has been hypothesized that low dose azacitidine may increase the graft-versus-leukemia effect and have a role in the maintenance of remission after allogeneic transplantation for myeloid leukemias. It is also intriguing that this favorable effect might occur while mitigating graft-versus-host disease. Here we present a review of the rapidly growing field of epigenetic manipulation using hypomethylating agents in allogeneic transplantation.
ISSN:1516-8484
1806-0870
1806-0870
DOI:10.5581/1516-8484.20130034