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  • Oncogenomics
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MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site

Oncogene volume 21, pages 4706–4714 (2002)Cite this article

Abstract

We examined the MLL translocation in two cases of infant AML with X chromosome disruption. The G-banded karyotype in the first case suggested t(X;3)(q22;p21)ins(X;11)(q22;q13q25). Southern blot analysis showed one MLL rearrangement. Panhandle PCR approaches were used to identify the MLL fusion transcript and MLL genomic breakpoint junction. SEPTIN6 from chromosome band Xq24 was the partner gene of MLL. MLL exon 7 was joined in-frame to SEPTIN6 exon 2 in the fusion transcript. The MLL genomic breakpoint was in intron 7; the SEPTIN6 genomic breakpoint was in intron 1. Spectral karyotyping revealed a complex rearrangement disrupting band 11q23. FISH with a probe for MLL confirmed MLL involvement and showed that the MLL-SEPTIN6 junction was on the der(X). The MLL genomic breakpoint was a functional DNA topoisomerase II cleavage site in an in vitro assay. In the second case, the karyotype revealed t(X;11)(q22;q23). Southern blot analysis showed two MLL rearrangements. cDNA panhandle PCR detected a transcript fusing MLL exon 8 in-frame to SEPTIN6 exon 2. MLL and SEPTIN6 are vulnerable to damage to form recurrent translocations in infant AML. Identification of SEPTIN6 and the SEPTIN family members hCDCrel and MSF as partner genes of MLL suggests a common pathway to leukaemogenesis.

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Acknowledgements

The AML Cell Bank of the Children's Cancer Group supplied specimens used in this research. CA Felix was supported by NIH Grants CA80175, CA77683, CA85469, Leukemia and Lymphoma Society Translational Research Award, and the Joshua Kahan Foundation. N Osheroff was supported by NIH Grant GM33944. E Hilgenfeld was supported by a postdoctoral fellowship from the Deutsche Krebshilfe. The authors thank Hesed Padilla-Nash and Turid Knutsen for valuable discussions and Nicole McNeil for technical assistance.

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Author notes

  1. Eva Hilgenfeld

    Present address: Hematology/Oncology, Medizinische Klinik und Poliklinik A, University of Muenster, Germany

  2. Brian D Lovett

    Present address: Pennsylvania State University College of Medicine, Hershey, 17033, PA, USA

  3. Reshma S Autar

    Present address: University of Amsterdam of the Medical Faculty of the Academic Medical Center of Amsterdam, The Netherlands

Authors and Affiliations

  1. Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, PA, USA

    Diana J Slater, Wendy Reed Williams, Brian D Lovett, Reshma S Autar & Carolyn A Felix

  2. Joseph Stokes Jr, Research Institute, Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, PA, USA

    Eric F Rappaport

  3. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, PA, USA

    Carolyn A Felix

  4. Genetics Division, National Cancer Institute, Bethesda, 20892, Maryland, MD, USA

    Eva Hilgenfeld & Thomas Ried

  5. Division of Hematology/Oncology, Department of Pediatrics, Geisinger Medical Center, Danville, 17822, Pennsylvania, PA, USA

    Narayan Shah

  6. Division of Hematology/Oncology, Department of Pediatrics, Alfred I Dupont Institute, Wilmington, 19899, Delaware, DE, USA

    Rita G Meek

  7. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, 37232, Tennessee, TN, USA

    Neil Osheroff

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  1. Diana J Slater
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Correspondence to Carolyn A Felix.

Additional information

The sequences reported in this study were deposited in the GenBank database (accession nos. AF512942, AF512943, AF512944, AF512945, AF512946).

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Slater, D., Hilgenfeld, E., Rappaport, E. et al. MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site. Oncogene 21, 4706–4714 (2002). https://doi.org/10.1038/sj.onc.1205572

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