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Workshop on Minimal Residual Disease

Rapid isolation of chromosomal breakpoints from patients with t(4;11) acute lymphoblastic leukemia: implications for basic and clinical research

Leukemia volume 15, pages 286–288 (2001)Cite this article

Chromosomal translocations t(4;11)(q21;q23) belong to the group of ‘11q23-translocations’ involving the MLL gene on chromosome 11 (also named ALL-1 or H RX).123 MLL has been shown to translocate to as many as 40 different loci, approximately half of them have been cloned so far and represent largely heterogeneous partner genes. The reciprocal chromosomal translocation t(4;11) is frequently found in early childhood in association with high-risk acute lymphoblastic leukemia, poor prognosis and highest incidence for disease onset in the first year of the patient's life. Thus, a rapid identification of this particular MLL translocation is of great importance and has prognostic and therapeutic consequences.

The common approach to detect MLL translocations is to perform RT-PCR analysis and to test for the presence of specific fusion transcripts that were generated after in-frame fusion of MLL to one of its many partner genes. Alternatives are (1) Southern blot experiments using MLL-specific cDNA probes; (2) FISH experiments using PAC or YAC probes spanning the MLL gene; or (3) to perform karyotype analysis of leukemic blasts. All these methods have their specific experimental limitations. However, the combined results of different experiments reliably allow identification of leukemia patients with such MLL translocations.

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References

  1. Ziemin van der Poel S, McCabe NR, Gill HJ, Espinosa III R, Patel Y, Harden A, Rubinelli P, Smith SD, LeBeau MM, Rowley JD, Diaz MO . Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias Proc Natl Acad Sci USA 1991 88: 10735–10739

    Article  CAS  Google Scholar 

  2. Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Croce CM, Canaani E . The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF4 gene Cell 1992 71: 701–708

    Article  CAS  Google Scholar 

  3. Tkachuk DC, Kohler S, Cleary ML . Involvement of a homolog of Drosophila-trithorax by 11q23 chromosomal translocations in acute leukemias Cell 1992 71: 691–700

    Article  CAS  Google Scholar 

  4. Leis T, Repp R, Borkhardt A, Metzler M, Schläger F, Harbott J, Lampert F . A new fingerprint method for sequence analysis of chromosomal translocations at the genomic DNA level Leukemia 1998 12: 758–763

    Article  CAS  Google Scholar 

  5. Nilson I, Löchner K, Siegler G, Greil J, Beck JD, Fey GH, Marschalek R . The exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukemias Br J Haematol 1996 93: 966–972

    Article  CAS  Google Scholar 

  6. Marschalek R, Nilson I, Löchner K, Greim R, Siegler G, Greil J, Beck JD, Fey GH . The structure of the human ALL-1/MLL/HRX gene Leuk Lymphoma 1997 27: 417–428

    Article  CAS  Google Scholar 

  7. Nilson I, Reichel M, Ennas M-G, Greim R, Knörr C, Siegler G, Greil J, Fey GH . Marschalek R. The exon/intron structure of the human AF4 gene, a member of the AF4/LAF4/FMR-2 gene family coding for a nuclear protein with structural alterations in acute leukemia Br J Haematol 1997 98: 157–169

    Article  CAS  Google Scholar 

  8. Gu Y, Alder H, Nakamura T, Schichman SA, Prasad R, Canaani O, Saito H, Croce CM, Canaani E . Sequence analysis of the breakpoint cluster region in the ALL-1 gene involved in acute leukemia Cancer Res 1994 54: 2327–2330

    CAS  Google Scholar 

  9. Marschalek R, Greil J, Löchner K, Nilson I, Siegler G, Zweckbronner I, Beck JD, Fey GH . Molecular analysis of the chromosomal breakpoint and fusion transcripts in the acute lymphoblastic SEM cell line with chromosomal translocation t(4;11) Br J Haematol 1995 90: 308–320

    Article  CAS  Google Scholar 

  10. Reichel M, Gillert E, Breitenlohner I, Repp R, Greil J, Beck JD, Fey GH, Marschalek R . Rapid isolation of chromosomal breakpoints from patient with t(4;11) acute lymphoblastic leukemia:implications for basic and clinical research Cancer Res 1999 59: 3357–3362

    CAS  Google Scholar 

  11. Gillert E, Leis T, Repp R, Reichel M, Hösch A, Breitenlohner I, Angermüller S, Borkhardt A, Harbott J, Lampert F, Griesinger F, Greil J, Fey GH, Marschalek R . A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells Oncogene 1999 18: 4663–4671

    Article  CAS  Google Scholar 

  12. Reichel M, Gillert E, Nilson I, Siegler G, Greil J, Fey GH, Marschalek R . Fine structure of translocation breakpoints in leukemic blasts with chromosomal translocation t(4;11): the damage-repair model of translocation Oncogene 1998 17: 3035–3044

    Article  CAS  Google Scholar 

  13. Gale KB, Ford AM, Repp R, Borkhardt A, Keller C, Eden OB, Greaves MF . Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots Proc Natl Acad Sci USA 1997 94: 13950–13954

    Article  CAS  Google Scholar 

  14. Fasching K, Panzer S, Haas OA, Marschalek R, Gadner H, Panzer-Grümayer R . Presence of clone-specific antigen receptor gene rearrangements at birth indicates an in utero origin of diverse types of early childhood ALL Blood 2000 95: 2722–2724

    CAS  Google Scholar 

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Acknowledgements

This work was supported by grants SFB 466-C4 from the Deutsche Forschungsgemeinschaft (DFG) and grant 96.047.3 from the Wilhelm Sander-Foundation.

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  1. Department of Paediatrics, Chair of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany

    M Reichel, E Gillert, I Breitenlohner, S Angermüller, GH Fey, R Marschalek, R Repp, J Greil & JD Beck

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Reichel, M., Gillert, E., Breitenlohner, I. et al. Rapid isolation of chromosomal breakpoints from patients with t(4;11) acute lymphoblastic leukemia: implications for basic and clinical research. Leukemia 15, 286–288 (2001). https://doi.org/10.1038/sj.leu.2402018

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