Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Molecular cytogenetics

Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia

Abstract

The t(10;11)(p13;q14–21) is a non-random translocation described in acute lymphoblastic and myeloid leukaemias. It results in the fusion of the gene CALM, which encodes a clathrin assembly protein, on 11q14 to the gene AF10, a putative transcription factor on 10p13. Here we describe for the first time, the occurrence of a CALM-AF10 fusion in a case of acute megakaryoblastic leukaemia. Fluorescence in situ hybridisation and reverse transcriptase polymerase chain reaction were used to confirm the presence of a CALM-AF10 fusion. A novel splice variant of CALM missing nt 1927–2091 was also detected. Though CALM is a cytoplasmic protein, the chimaeric fusion product is able to localise to both the nucleus and cytoplasm. Analysis of the fusion variants suggests, however, that the critical fusion product is likely to be cytoplasmic and contain the interactive leucine zipper of AF10.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Chaplin T, Ayton P, Bernard OA, Saha V, Della Valle V, Hillion J, Gregorini A, Lillington D, Berger R, Young BD . A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia Blood 1995 85: 1435–1441

    CAS  PubMed  Google Scholar 

  2. Dreyling MH, Martinez-Climent JA, Zheng M, Mao J, Rowley JD, Bohlander SK . The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family Proc Natl Acad Sci USA 1996 93: 4804–4809

    Article  CAS  Google Scholar 

  3. Young BD, Saha V . Chromosome abnormalities in leukaemia: the 11q23 paradigm Cancer Surv 1996 28: 225–245

    CAS  PubMed  Google Scholar 

  4. Saha V, Young BD, Freemont PS . Translocations, fusion genes, and acute leukemia J Cell Biochem 1998 3: 264–276

    Article  Google Scholar 

  5. Saha V, Chaplin T, Gregorini A, Ayton P, Young BD . The leukemia-associated protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins Proc Natl Acad Sci USA 1995 92: 9737–9741

    Article  CAS  Google Scholar 

  6. Linder B, Newman R, Jones LK, Debernardi S, Young BD, Freemont P, Verrijzer CP, Saha V . Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation J Mol Biol 2000 299: 369–378

    Article  CAS  Google Scholar 

  7. Linder B, Jones LK, Chaplin T, Mohd-Sarip A, Heinlein UA, Young BD, Saha V . Expression pattern and cellular distribution of the murine homologue of AF10 Biochim Biophys Acta 1998 1443: 285–296

    Article  CAS  Google Scholar 

  8. Tebar F, Bohlander SK, Sorkin A . Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic Mol Biol Cell 1999 10: 2687–2702

    Article  CAS  Google Scholar 

  9. Bohlander SK, Muschinsky V, Schrader K, Siebert R, Schlegelberger B, Harder L, Schemmel V, Fonaysch C, Ludwig WD, Hiddemann W, Dreyling MH . Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients Leukemia 2000 14: 93–99

    Article  CAS  Google Scholar 

  10. Carlson KM, Vignon C, Bohlander S, Martinez-Climent JA, Le Beau MM, Rowley JD . Identification and molecular characterization of CALM/AF10 fusion products in T cell acute lymphoblastic leukemia and acute myeloid leukemia Leukemia 2000 14: 100–104

    Article  CAS  Google Scholar 

  11. Dreyling MH, Schrader K, Fonatsch C, Schlegelberger B, Haase D, Schoch C, Ludwig W, Loffler H, Buchner T, Wormann B, Hiddemann W, Bohlander SK . MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis Blood 1998 91: 4662–4467

    CAS  PubMed  Google Scholar 

  12. Kobayashi H, Hosoda F, Maseki N, Sakurai M, Imashuku S, Ohki M, Kaneko Y . Hematologic malignancies with the t(10;11)(p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes Genes Chromos Cancer 1997 20: 253–259

    Article  CAS  Google Scholar 

  13. Kumon K, Kobayashi H, Maseki N, Sakashita A, Sakurai M, Tanizawa A, Imashuku S, Kaneko, Y . Mixed-lineage leukemia with t(10;11)(p13;q21): an analysis of AF10-CALM and CALM-AF10 fusion mRNAs and clinical features Genes Chromos Cancer 1999 25: 33–39

    Article  CAS  Google Scholar 

  14. Narita M, Shimizu K, Hayashi Y, Taki T, Taniwaki M, Hosoda F, Kobayashi H, Nakamura H, Sadamori N, Ohnishi H, Bessho F, Yanagisawa M, Ohki M . Consistent detection of CALM-AF10 chimaeric transcripts in haematological malignancies with t(10;11)(p13;q14) and identification of novel transcripts Br J Haematol 1999 105: 928–937

    Article  CAS  Google Scholar 

  15. Silliman CC, McGavran L, Wei Q, Miller LA, Li S, Hunger SP . Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13–14;q14–q21) suggests a potential role for truncated AF10 polypeptides Leukemia 1998 12: 1404–1410

    Article  CAS  Google Scholar 

  16. Rooney DE, Czepulkowski BH . Lymphocyte culture In: Constitutional Analysis, 2nd edn Oxford University Press: Oxford 1992 pp 31–54

    Google Scholar 

  17. Richards MW, Behrens RH, Doherty JF . Short report: hematologic changes in acute, imported Plasmodium falciparum malaria Am J Trop Med Hyg 1998 59: 859

    Article  CAS  Google Scholar 

  18. Borkhardt A, Haas OA, Strobl W, Repp R, Mann G, Gadner H, Lampert F . A novel type of MLL/AF10 fusion transcript in a child with acute megakaryocytic leukemia (AML-M7) Leukemia 1995 9: 1796–1797

    CAS  PubMed  Google Scholar 

  19. Lion T, Haas OA, Harbott J, Bannier E, Ritterbach J, Jankovic M, Fink FM, Stojimirovic A, Herrmann J, Riehm HJ . The translocation t(1;22)(p13;q13) is a nonrandom marker specifically associated with acute megakaryocytic leukemia in young children Blood 1992 79: 3325–3330

    CAS  PubMed  Google Scholar 

  20. Chaplin T, Bernard O, Beverloo HB, Saha V, Hagemeijer A, Berger R, Young BD . The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene Blood 1995 86: 2073–2076

    CAS  PubMed  Google Scholar 

  21. Beverloo HB, Le Coniat M, Wijsman J, Lillington DM, Bernard O, de Klein A, van Wering E, Welborn J, Young BD, Hagemeijer A, Berger R . Breakpoint heterogeneity in t(10;11) translocation in AML-M4/M5 resulting in fusion of AF10 and MLL is resolved by fluorescent in situ hybridization analysis Cancer Res 1995 55: 4220–4224

    CAS  PubMed  Google Scholar 

  22. Chaplin T, Jones LK, Debernardi S, Hill AS, Lillington DM, Young BD . Molecular analysis of the genomic inversion and insertion of AF10 into MLL suggests a single step event Genes Chromos Cancer 2001 30: 175–180

    Article  CAS  Google Scholar 

  23. Lillington DM, Jaju RJ, Shankar AG, Neat M, Kearney L, Young BD, Saha V . Cytogenetic and molecular evidence of marrow involvement in extramedullary acute myeloid leukaemia Br J Haematol 2000 110: 547–551

    Article  CAS  Google Scholar 

Download references

Acknowledgements

AS was supported by a grant from the Joint Research Board of St Bartholomew's Hospital. We wish to thank Professor JS Lilleyman for reviewing the marrow slides.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, L., Chaplin, T., Shankar, A. et al. Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia. Leukemia 15, 910–914 (2001). https://doi.org/10.1038/sj.leu.2402140

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402140

Keywords

This article is cited by

Search

Quick links