Your browser doesn't support javascript.
loading
Promoter Hypomethylation and Expression Is Conserved in Mouse Chronic Lymphocytic Leukemia Induced by Decreased or Inactivated Dnmt3a.
Haney, Staci L; Upchurch, G Michael; Opavska, Jana; Klinkebiel, David; Hlady, Ryan A; Suresh, Abhinav; Pirruccello, Samuel J; Shukla, Vipul; Lu, Runqing; Costinean, Stefan; Rizzino, Angie; Karpf, Adam R; Joshi, Shantaram; Swanson, Patrick; Opavsky, Rene.
Affiliation
  • Haney SL; Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Upchurch GM; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Opavska J; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Klinkebiel D; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Hlady RA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
  • Suresh A; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Pirruccello SJ; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Center for Leukemia and Lymphoma Research, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Shukla V; Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Lu R; Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Costinean S; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Rizzino A; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Pathology and
  • Karpf AR; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Joshi S; Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA; Center for Leukemia and Lymphoma Research, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Swanson P; Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE 68102, USA.
  • Opavsky R; Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; Center for Leukemia and Lym
Cell Rep ; 15(6): 1190-201, 2016 05 10.
Article in En | MEDLINE | ID: mdl-27134162
ABSTRACT
DNA methyltransferase 3a (DNMT3A) catalyzes the formation of 5-methyl-cytosine in mammalian genomic DNA, and it is frequently mutated in human hematologic malignancies. Bi-allelic loss of Dnmt3a in mice results in leukemia and lymphoma, including chronic lymphocytic leukemia (CLL). Here, we investigate whether mono-allelic loss of Dnmt3a is sufficient to induce disease. We show that, by 16 months of age, 65% of Dnmt3a(+/-) mice develop a CLL-like disease, and 15% of mice develop non-malignant myeloproliferation. Genome-wide methylation analysis reveals that reduced Dnmt3a levels induce promoter hypomethylation at similar loci in Dnmt3a(+/-) and Dnmt3a(Δ/Δ) CLL, suggesting that promoters are particularly sensitive to Dnmt3a levels. Gene expression analysis identified 26 hypomethylated and overexpressed genes common to both Dnmt3a(+/-) and Dnmt3a(Δ/Δ) CLL as putative oncogenic drivers. Our data provide evidence that Dnmt3a is a haplo-insufficient tumor suppressor in CLL and highlights the importance of deregulated molecular events in disease pathogenesis.
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia, Lymphocytic, Chronic, B-Cell / Gene Expression Regulation, Leukemic / Promoter Regions, Genetic / DNA Methylation / DNA (Cytosine-5-)-Methyltransferases Limits: Animals / Humans Language: En Journal: Cell Rep Year: 2016 Document type: Article Affiliation country:
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia, Lymphocytic, Chronic, B-Cell / Gene Expression Regulation, Leukemic / Promoter Regions, Genetic / DNA Methylation / DNA (Cytosine-5-)-Methyltransferases Limits: Animals / Humans Language: En Journal: Cell Rep Year: 2016 Document type: Article Affiliation country: