title: CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12.
abstract: The t(10;11)(p12;q14) is a recurring chromosomal translocation that gives rise to the CALM/AF10 fusion gene, which is found in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma. We analyzed the fusion transcripts in 20 new cases of CALM/AF10-positive leukemias, and compared the gene expression profile of 10 of these to 125 patients with other types of leukemia and 10 normal bone marrow samples. Based on gene set enrichment analyses, the CALM/AF10-positive samples showed significant upregulation of genes involved in chromatin assembly and maintenance and DNA repair process, and downregulation of angiogenesis and cell communication genes. Interestingly, we observed a striking upregulation of four genes located immediately centromeric to the break point of the t(10;11)(p12;q14) on 10p12 (COMMD3 (COMM domain containing 3), BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), DNAJC1 (DnaJ (Hsp40) homolog subfamily C member 1) and SPAG6 (sperm associated antigen 6)). We also conducted semiquantitative reverse transcriptase-PCR analysis on leukemic blasts from a murine CALM/AF10 transplantation model that does not have the translocation. Commd3, Bmi1 and Dnajc1, but not Spag6 were upregulated in these samples. These results strongly indicate that the differential regulation of these three genes is not due to the break point effect but as a consequence of the CALM/AF10 fusion gene expression, though the mechanism of regulation is not well understood.
authors: Department of Internal Medicine III, Großhadern, Ludwig Maximilians University and HelmholtzZentrum Muenchen, Clinical Cooperative Group Leukemia, Munich, Germany.
authors: M A
authors: MA
authors: Mulaw
authors: A
authors: A
authors: Krause
authors: A J
authors: AJ
authors: Krause
authors: A J
authors: AJ
authors: Deshpande
authors: L F
authors: LF
authors: Krause
authors: A
authors: A
authors: Rouhi
authors: R
authors: R
authors: La Starza
authors: A
authors: A
authors: Borkhardt
authors: C
authors: C
authors: Buske
authors: C
authors: C
authors: Mecucci
authors: W-D
authors: WD
authors: Ludwig
authors: C
authors: C
authors: Lottaz
authors: S K
authors: SK
authors: Bohlander
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D043283:Chromosome Fragile Sites; D002879:Chromosomes, Human, Pair 10; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D051379:Mice; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D015854:Up-Regulation
chemical_list: C092513:MLLT10 protein, human; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D014157:Transcription Factors