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Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10,16)(q22,p13)
Dept of Clin Genetics Lund.
Dept of Clin Genetics, Lund.
Dept of Clin Genetics, Lund.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
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2001 (English)In: Human Molecular Genetics, ISSN 0964-6906, Vol. 10, no 4, 395-404 p.Article in journal (Refereed) Published
Abstract [en]

The CBP gene at 16p 13 fuses to MOZ and MLL as a result of the t(8,16)(p11,p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11,16)(q23,p13) in treatment-related AML, respectively. We show here that a novel t(10,16)(q22,p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.

Place, publisher, year, edition, pages
2001. Vol. 10, no 4, 395-404 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-30291Local ID: 15814OAI: diva2:251113
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2011-01-13

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Samuelsson, Ulf
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Faculty of Health SciencesPediatricsDepartment of Paediatrics in Linköping
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