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Oncogenes, Fusion Genes and Tumor Suppressor Genes

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

Leukemia volume 26, pages 1012–1019 (2012)Cite this article

A Corrigendum to this article was published on 12 December 2012

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.

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Acknowledgements

We acknowledge Claudia Haferlach, Torsten Haferlach, Susanne Schnittger and Alexander Kohlmann for contributing patient samples and some of the expression data to this work. We are thankful to Stefan Bentink and Reiner Spang for developing R scripts for this analysis. A Krause and M Mulaw were supported by a DAAD (German Academic Exchange Service) exchange fellowship. C Lottaz was supported by the BMBF (Leukemia Net). C Buske received support from the Deutsche Forschungsgemeinschat (SFB 684-A8). This work was supported by grants from the German Ministry of Research and Education (Leukemia net, BMBF; 01GS0448) and the Deutsche Forschungsgemeinschaft (SFB 684-A6) to SK Bohlander.

Author contributions

SKB designed the experiments and the study; AJK did sample preparation for microarray study and sequencing; MAM and SKB did the statistical data analysis and interpretation of the microarray results; MAM, AJK and SKB wrote the manuscript; CB, AJD and AR provided the CALM/AF10 bone marrow transplantation model samples for RT-PCR, which was done by AJK; RLS, AB, CM and WDL provided patient samples; CL helped in statistical data analysis.

Author information

Author notes

  1. A J Krause & L F Krause

    Present address: 9Current address: Hematology Division, Department of Internal Medicine, University of São Paulo, Campus USP, Ribeirão Preto, SP, Brazil,

  2. A J Deshpande

    Present address: 10Current address: Children's Hospital Boston, Harvard Medical School, Boston MA, USA,

  3. M A Mulaw and A J Krause: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Internal Medicine III, Großhadern, Ludwig Maximilians University and HelmholtzZentrum Muenchen, Clinical Cooperative Group Leukemia, Munich, Germany

    M A Mulaw, A J Krause, A J Deshpande, L F Krause & S K Bohlander

  2. Institute of Experimental Oncology, CCCU & Ulm University Hospital, Ulm, Germany

    A Rouhi & C Buske

  3. University Hospital S. Maria della Misericordia, Perugia, Italy

    R La Starza & C Mecucci

  4. Department of Pediatric Oncology, Hematology and Clinical Immunology, Centre for Child and Adolescent Health, Heinrich Heine University, Düsseldorf, Germany

    A Borkhardt

  5. Immunologic Marker Laboratory, Charite University Hospital, Berlin, Germany

    W-D Ludwig

  6. Institute for Functional Genomics, University of Regensburg, Regensburg, Germany

    C Lottaz

  7. Department of Internal Medicine III, Laboratory for Leukemia Diagnostics, Großhadern, Ludwig Maximilians University, Munich, Germany

    S K Bohlander

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  1. M A Mulaw
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Correspondence to S K Bohlander.

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Mulaw, M., Krause, A., Deshpande, A. et al. 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. Leukemia 26, 1012–1019 (2012). https://doi.org/10.1038/leu.2011.307

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