Mulaw, M. A. and Krause, A. J. and Deshpande, A. J. and Krause, L. F. and Rouhi, A. and La Starza, R. and Borkhardt, A. and Buske, C. and Mecucci, C. and Ludwig, W-D and Lottaz, C. and Bohlander, S. K. (2012) 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 (5). pp. 1012-1019. ISSN 0887-6924,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; CALM-AF10 FUSION GENE; BONE-MARROW; INCREASED ANGIOGENESIS; EXPRESSION PROFILES; TRANSGENIC MICE; HISTONE H3K4ME3; T-ALL; CALM/AF10; microarray; GSEA; myeloid and lymphoid neoplasia; genomic instability and DNA repair |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 May 2020 05:39 |
| Last Modified: | 15 May 2020 05:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18797 |
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