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A trithorax–like gene is interrupted by chromosome 11q23 translocations in acute leukaemias

An Erratum to this article was published on 01 August 1993

Abstract

Some acute lymphocytic leukaemias, particularly those in young children, are associated with a t(4;11)(q21;q23) reciprocal translocation. We have cloned the translocation breakpoint on chromosome 11q23 and isolated corresponding RNA transcripts from this region. The translocation occurs within a cluster of Alu repetitive elements located within an intron of a gene that gives rise to 11.5 (kb) transcript spanning the translocation breakpoint. The 11.5 kb transcript encodes a protein that is highly homologous to the Drosophila trithorax gene, a developmental regulator. An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region.

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References

  1. Berger, R. et al. Acute Monocytic Leukaemia chromosome studies. Leukemia Res. 6, 17–26 (1982).

    Article  CAS  Google Scholar 

  2. Arthur, D.C., Bloomfield, C.D., Lindquist, L.L. & Nesbit, M.E. Translocation 4;11 in acute lymphoblastic leukaemia: Clinical characteristics and prognostic significance. Blood 59, 96–99 (1982).

    CAS  PubMed  Google Scholar 

  3. Hagemeijer, A. et al. Characterization of the blast cells in acute leukaemia with translocation (4;11): report of eight additional cases and of one case with a variant translocation. Leukemia 1, 24–31 (1987).

    CAS  PubMed  Google Scholar 

  4. Sait, S.N., Raza, A. & Sanberg, A.A. A t(1;11) in acute nonlymphocytic leukaemia FAB type M4. Cancer Genet. Cytogenet. 24, 181–183 (1987).

    Article  CAS  Google Scholar 

  5. Feder, M., Finan, J., Besa, J. & Nowell, P. A2p;11q chromosome translocation in dysmyelopoietic preleukaemia. Cancer Genet. Cytogenet. 15, 143–150 (1985).

    Article  CAS  Google Scholar 

  6. Derre, J., Cherif, D., Le Coniat, M., Julier, C. & Berger, R. In situ hybridization ascertains the presence of a translocation t(6;11) in an acute monocytic leukaemia. Gene chromosom. Cancer 2, 341–344 (1990).

    Article  CAS  Google Scholar 

  7. Hagemeijer, A., Hahlen, K., Sizoo, W. & Abels, J. Translocation (9;11 )(p21;q23) in three cases of acute monoblastic leukaemia. Cancer Genet. Cytogenet., 5, 95–105 (1982).

    Article  CAS  Google Scholar 

  8. Pui, C.H. et al. An analysis of leukemic cell chromosomal features in infants. Blood 69, 1289–1293 (1987).

    CAS  PubMed  Google Scholar 

  9. Abe, R., Ryan, D., Cecalupo, A., Cohen, H. & Sandberg, A.A. Cytogenetic findings in congenital leukaemia: Case report and review of the literature. Cancer Genet. Cytogenet. 9, 139–144 (1983).

    Article  CAS  Google Scholar 

  10. Chuu, W.M. et al. Infant leukaemia: an analysis of nine Chinese patients. Am. J. Hematol. 34, 246–251 (1990).

    Article  CAS  Google Scholar 

  11. Gibbons, B., Katz, F.E., Ganly, P. & Chessels, J.M. Infant acute leukaemia with t(11;19). Br. J. Hematol. 74, 264–269 (1990).

    Article  CAS  Google Scholar 

  12. Rowley, J.D. et al. Mapping chromosome band 11q23 in human acute leukaemia with biotinilated probes : Identification of 11q23 translocation breakpoints with yeast artificial chromosome. Proc. natn. Acad. Sci. U.S.A. 87, 9358–9362 (1990).

    Article  CAS  Google Scholar 

  13. Cimino, G. et al. Cloning of ALL1, the locus involved in leukaemia with the t(4;11)(q21;q23),t(9;11)(p22;q23), and t(11;19)(q23;p1) chromosome translocation. Cancer Res. 51, 6712–6714 (1991).

    CAS  Google Scholar 

  14. Ziemin-van der Poel, S. et al. Identification of a gene, MLL1, that span the breakpoint in 11q23 translocation associated with human leukaemias. Proc. natn. Acad. Sci. U.S.A. 88, 10735–10739 (1991).

    Article  CAS  Google Scholar 

  15. Cimino, G. et al. An altered 11-kilobase transcript in leukemic cell lines with the t(4;11)(q21;q23) chromosome translocation. Cancer Res. 52, 3811–3813 (1992).

    CAS  PubMed  Google Scholar 

  16. Evans, G.A. & Lewis, K.A. Physical mapping of complex genomes by cosmid multiplex analysis. Proc. natn. Acad. Sci. U.S.A. 86, 5030–5034 (1989).

    Article  CAS  Google Scholar 

  17. Lichter, P. et al. Hight resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 85, 9664–9668 (1990).

    Google Scholar 

  18. Chen, C.S., Medberry, P.S., Arthur, D.C. & Kersey, J.H. Breakpoint clustering in t(4;11)(q21;q23) acute leukaemia. Blood 78, 2498–2504 (1991).

    CAS  PubMed  Google Scholar 

  19. Browstein, B.H. et al. Isolation of single copy human genes from a library of yeast artificial chromosomes clones. Science 244, 1348–1351 (1989).

    Article  Google Scholar 

  20. Albertsen, H.M. et al. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalent Proc. Proc. natn. Acad. Sci. U.S.A. 87, 4256–4260 (1990).

    Article  CAS  Google Scholar 

  21. Djabali, M. et al. A simple method for the direct use of total cosmid clones as hybridization probes. Nucl. Acids Res. 20, 6789 (1990).

    Google Scholar 

  22. Stephen, F. Basic local alignment search tool. J. molec. Biol. 215, 403–410 (1990).

    Article  Google Scholar 

  23. Mazo, A.M., Huang, D., Mozer, A.B. & Dawid, I. The trithorax gene, a transacting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. Proc. natn. Acad. Sci. U.S.A. 87, 2112–2116 (1990).

    Article  CAS  Google Scholar 

  24. Van der Felz, M.J.M. et al. Nucleotide sequence of both reciprocal translocation junction regions in a patient with Ph positive acute lymphoblastic leukaemia, with a breakpoint within the first intron of the BCR gene. Nucl. Acids Res. 17, 1–10 (1989).

    Article  Google Scholar 

  25. Rouyer, F., Simmler, M.C., Page, D.C. & Weissenbach, J. A sex chromosome rearrangement in human XX male caused by Alu-Alu recombination. Cell 51, 417–425 (1987).

    Article  CAS  Google Scholar 

  26. Kearney, L. et al. Chromosome 11q23 translocations in both infant and adult acute leukaemias are detected by in situ hybridization with a yeast artificial chromosome. Blood (in the press).

  27. Stong, R.C. et al. Human acute leukaemiacell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics. Blood 65, 21–31 (1985).

    CAS  Google Scholar 

  28. Konsuwan, K., Webb, E., Housiaux, P. & Adams, J.M. Expression of multiple homeobox genes within divers hematopoietic lineages. EMBO J., 7, 2131–2136 (1988).

    Article  Google Scholar 

  29. Shen, W.F., Detmer, K., Simonitch-Eason, T.A., Lawrence, H.J. & Largman, C. Alternative splicing of the HOX 2.2 homeobox gene in human hemapoietic cells and murine embryonic and adult tissues. Nucl. Acids Res. 19, 539–544 (1991).

    Article  CAS  Google Scholar 

  30. Dubbe, I.D. et al. A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14). Blood 78, 2996–3003 (1991).

    Google Scholar 

  31. Hatano, M., Roberts, C.M., Minden, M., Crist, W.M. & Korsmeyer, S.J. Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukaemia. Science 253, 79–82 (1991).

    Article  CAS  Google Scholar 

  32. McGuire, E.A. et al. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts,including Ttg-1 a gene encoding a potential zinc finger protein. Molec. Cell Biol. 9, 2124–2130 (1989).

    Article  CAS  Google Scholar 

  33. Kamps, M.P., Murre, C., Sun, X.-H. & Baltimore, D. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell 60, 547–562 (1990).

    Article  CAS  Google Scholar 

  34. Kamps, M.P., Look, T.A. & Baltimore, D. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev. 5, 353–358 (1991).

    Article  Google Scholar 

  35. Green, E.D. & Olson, M.V. Systematic screening of yeast artificial chromosome libraries using the polymerase chain reaction. Proc. natn. Acad. Sci. U.S.A. 87, 1213–1217 (1990).

    Article  CAS  Google Scholar 

  36. Benton, W.D. & Davis, R.W. Screening λgt recombinant clones by hybridization to single plaques in situ. Science 196, 180–182 (1977).

    Article  CAS  Google Scholar 

  37. Selleri, L., Hermanson, G., Eubanks, J.H., Lewis, K.A. & Evans, G. Molecular localization of the 11q24;22q12 translocation of Ewings's sarcoma by Chromosomal in situ suppression hybridization. Proc. natn. Acad. Sci. U.S.A. 88, 887–891 (1990).

    Article  Google Scholar 

  38. Evans, G., Lewis, K.A. & Lawless, G.M. Molecular organization of the human CDS gene family on chromosome 11q23. Immunogenetics 28, 365–373 (1988).

    Article  CAS  Google Scholar 

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Djabali, M., Selleri, L., Parry, P. et al. A trithorax–like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet 2, 113–118 (1992). https://doi.org/10.1038/ng1092-113

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