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Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14)

Oncogene volume 22, pages 1418–1424 (2003)Cite this article

Abstract

Translocations interrupting the mixed lineage leukemia gene (MLL) occur in 7–10% of acute lymphoblastic leukemia (ALL) and 5–6% of acute myeloid leukemia (AML) cases. One of these translocations, t(11;15)(q23;q14), occurs rarely in both ALL and AML. The gene on chromosome 15, AF15q14, was cloned recently in a patient with AML-M4. We have identified the same gene in a de novo T-ALL patient. However, both the MLL and AF15q14 breakpoints in these patients differed: in the previously reported AML-M4, both gene breaks were within exons, while in our ALL case the MLL break is intronic and the AF15q14 break is exonic. The MLL–AF15q14 fusion described previously shares no AF15q14 residues in common with the chimera reported here. The fusion proteins also differ with respect to MLL – the previously described fusion contains 55 extra amino acids as its MLL break is in exon 11, while the chimera we report breaks in intron 9. Contrary to the originally described normal AF15q14 (5925-bp cDNA encoding a 1833-aa protein), we identify a 7542-bp cDNA and a 2342-aa AF15q14 protein. AF15q14 appears identical to an mRNA previously found to be expressed in melanoma rendered nontumorigenic by microcell-mediated introduction of normal chromosome 6, suggesting the gene may function normally to suppress cell growth and/or enhance maturation.

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Acknowledgements

We thank Dr Ruth Rimokh for constructive comments regarding our studies. We thank Dr Janet D Rowley for sharing unpublished data and for her support during the course of this work. Dr Xiaoli Cui provided excellent technical assistance. This work was supported by grant CA76301 (SWM) and Cancer Center Support (CORE) grant CA21765 from the National Cancer Institute, by the American Lebanese Syrian Associated Charities (ALSAC), St Jude Children's Research Hospital, by a postdoctoral fellowship from the Leukemia Research Foundation (VC) and a Cancer Biology Training Grant (VC), and by grants CA40046 and CA78438 (NJZ-L).

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Author notes

  1. Nancy J Zeleznik-Le

    Present address: Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, USA

  2. Martin U Kuefer and Vandana Chinwalla: Both authors contributed equally to this work.

Authors and Affiliations

  1. Abteilung Gesundheitswesen, Landratsamt Ostallgäu, Postfach 1255, Marktoberdorf, 87610, Germany

    Martin U Kuefer

  2. Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA

    Vandana Chinwalla & Nancy J Zeleznik-Le

  3. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    Frederick G Behm, Susana C Raimondi & Stephan W Morris

  4. Hartwell Center for Biotechnology, St Jude Children's Research Hospital, Memphis, TN, USA

    Clayton W Naeve, Karen M Rakestraw & Suraj T Mukatira

  5. Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN, USA

    Stephan W Morris

  6. University of Tennessee, College of Medicine, Memphis, TN, USA

    Frederick G Behm, Susana C Raimondi & Stephan W Morris

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  1. Martin U Kuefer
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Correspondence to Stephan W Morris.

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Kuefer, M., Chinwalla, V., Zeleznik-Le, N. et al. Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14). Oncogene 22, 1418–1424 (2003). https://doi.org/10.1038/sj.onc.1206272

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