Histone methyltransferase Suv39h1 deficiency prevents Myc‐induced chromosomal instability in murine myeloid leukemias1. Issue 4 (23rd January 2013)

• Record Type: Journal Article
• Authors: Vajen, Beate; Modlich, Ute; Schienke, Andrea; Wolf, Susanne; Skawran, Britta; Hofmann, Winfried; Büsche, Guntram; Kreipe, Hans; Baum, Christopher; Santos‐Barriopedro, Irene; Vaquero, Alejandro; Schlegelberger, Brigitte; Rudolph, Cornelia
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 4(2013:Apr.)
• Page Start: 423
• Page End: 430
• Publication Date: 2013-01-23
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22040
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Suv39h1 mediates heterochromatin formation in pericentric and telomeric regions by trimethylation of lysine 9 of histone 3 (H3K9me3). Yet, its role in the induction of chromosomal instability is poorly understood. We established a leukemia model by retrovirally expressing <italic>Myc</italic> in wild‐type and histone methyltransferase <italic>Suv39h1</italic>‐deficient hematopoietic cells and characterized the resulting leukemias for chromosomal instability. All mice that received cells overexpressing <italic>Myc</italic> developed myeloid leukemia with a median survival of 44 days posttransplantation. <italic>Myc</italic>‐overexpressing wild‐type leukemias demonstrated clones with numerical chromosomal aberrations (5/16). In secondary transplantations of these leukemic cells, structural changes, mostly end‐to‐end fusions of chromosomes, appeared (10/12). In contrast, leukemic cells overexpressing <italic>Myc</italic> with reduced or no <italic>Suv39h1</italic> expression had a normal karyotype in primary, secondary, and tertiary transplantations (16/16). <italic>Myc</italic>‐transduced <italic>Suv39h1</italic>‐deficient cells showed less critically short telomeres (<italic>P</italic> < 0.05) compared with <italic>Myc</italic>‐transduced wild‐type bone marrow cells. Gene expression analysis showed upregulation of genes involved in the alternative lengthening of telomeres (ALT) mechanism. Thus, we hypothesize that loss of Suv39h1 implies activation of the ALT mechanism, in turn ensuring telomere length and stability. Our data show for the first time that <italic>Suv39h1</italic> deficiency may prevent chromosomal instability by more efficient telomere stabilization in hematopoietic bone marrow cells overexpressing <italic>Myc</italic>. © 2013 Wiley Periodicals, Inc.</p> </abstract>