DNMT3B: Roles in Leukemia

Wed, 01/22/2014 - 12:55

DNA-methyltransferase 3B (DNMT3B), also known as DNA methyltransferase HsaIIIB, is a member of the class I-like SAM-binding methyltransferase superfamily and C5-methyltransferase family. DNMT3B plays an essential role in the establishment of DNA methylation patterns during development and is vital for genome-wide de novo methylation.

DNMT3B has been linked to two distinct types of leukemia in recent studies: acute myeloid leukemia (AML) and juvenile myelomonocytic leukemia (JMML).  In AML, myeloid blood cells become cancerous and cause rapid production of abnormal while blood cells in the bone marrow, which in turn, affects production of regular blood cells (1).  A mutation of the DNMT3B gene is frequently found in patients with AML (2).  Studies have found a correlation between overexpression of DNMT3B and prolonged survival in AML patients.  Overexpression of DNMT3B causes hypermethylation to the MLL-AF9 and c-myc/bcl2 sites in leukemia cells.  This hypermethylation to the exons and gene bodies resulted in down regulation of several cancer-associated genes. These genes play a role in cell growth and proliferation as well as maintenance and development of the hematopoietic system.  DNMT3B’s induced DNA methylation of the hematopoietic stem cells affects their phenotype and function resulting in inhibitory function in of leukemia initiation and maintenance.  Additional research is needed to identify differentially expressed DNMT3B target genes to further the advancement of potential new AML therapies.

Western Blot: Dnmt3b Antibody Western Blot: Dnmt3b Antibody

Juvenile myelomonocytic leukemia (JMML) is a cancer that occurs in infants and young children and typically results in death within a year.   JMML is a mixed myelodysplastic/myeloproliferative (MDS/MPD) disorder that is characterized by leukocytosis, monocytosis, hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), elevated fetal hemoglobin, absence of the Philadelphia chromosome (aka BCR/ABL fusion gene), and a low percentage of myeloblasts in bone marrow.  Pathogenesis is marked by hypermethylation on the PTEN promoter and mutations to the following genes: NF1, CBL, RAS, and PTPN11.  Recent studies have also suggested that hypermethylation to the CALCA, RARB, CDKN2B, and BMP4 promoters may also play a role in pathogenesis of JMML.  The hypermethylation of these promoters is linked to overexpression of DNMT3B protein.  In JMML, the overexpression of DNMT3B was also found to down regulate expression of micro RNA miR-29a on human chromosome 7q32. This inverse correlation shows that DNMT3B has the ability to create epigenetic modifications in developmental plasticity as well as direct changes to the methylation of various promoters (3).  Further research of DNMT3B and its epigenetic effects will hopefully offer a different strategy for future research into leukemia treatments and therapies.

  1. PMID:  11814064
  2. ISSN:  1528-0020
  3. ISSN: 1528-0020

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