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Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

Leukemia volume 18, pages 895–908 (2004)Cite this article

Abstract

Chromosome aberrations are frequently observed in precursor-B-acute lymphoblastic leukemias (ALL) and T-cell acute lymphoblastic leukemias (T-ALL). These translocations can form leukemia-specific chimeric fusion proteins or they can deregulate expression of an (onco)gene, resulting in aberrant expression or overexpression. Detection of chromosome aberrations is an important tool for risk classification. We developed rapid and sensitive split-signal fluorescent in situ hybridization (FISH) assays for six of the most frequent chromosome aberrations in precursor-B-ALL and T-ALL. The split-signal FISH approach uses two differentially labeled probes, located in one gene at opposite sites of the breakpoint region. Probe sets were developed for the genes TCF3 (E2A) at 19p13, MLL at 11q23, ETV6 at 12p13, BCR at 22q11, SIL-TAL1 at 1q32 and TLX3 (HOX11L2) at 5q35. In normal karyotypes, two colocalized green/red signals are visible, but a translocation results in a split of one of the colocalized signals. Split-signal FISH has three main advantages over the classical fusion-signal FISH approach, which uses two labeled probes located in two genes. First, the detection of a chromosome aberration is independent of the involved partner gene. Second, split-signal FISH allows the identification of the partner gene or chromosome region if metaphase spreads are present, and finally it reduces false-positivity.

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References

  1. Rowley JD . The role of chromosome translocations in leukemogenesis. Semin Hematol 1999; 36: 59–72.

    CAS  PubMed  Google Scholar 

  2. Look AT . Oncogenic transcription factors in the human acute leukemias. Science 1997; 278: 1059–1064.

    Article  CAS  PubMed  Google Scholar 

  3. Rabbitts TH . Chromosomal translocations in human cancer. Nature 1994; 372: 143–149.

    Article  CAS  PubMed  Google Scholar 

  4. Huret JL, Dessen P, Bernheim A . An atlas of chromosomes in hematological malignancies. Example: 11q23 and MLL partners. Leukemia 2001; 15: 987–989.

    Article  CAS  PubMed  Google Scholar 

  5. Aplan PD, Raimondi SC, Kirsch IR . Disruption of the SCL gene by a t(1;3) translocation in a patient with T cell acute lymphoblastic leukemia. J Exp Med 1992; 176: 1303–1310.

    Article  CAS  PubMed  Google Scholar 

  6. Carroll AJ, Crist WM, Link MP, Amylon MD, Pullen DJ, Ragab AH, Buchanan GR, Wimmer RS, Vietti TJ . The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1990; 76: 1220–1224.

    CAS  PubMed  Google Scholar 

  7. Fitzgerald TJ, Neale GA, Raimondi SC, Goorha RM . c-tal, a helix-loop-helix protein, is juxtaposed to the T-cell receptor-beta chain gene by a reciprocal chromosomal translocation: t(1;7)(p32;q35). Blood 1991; 78: 2686–2695.

    CAS  PubMed  Google Scholar 

  8. Francois S, Delabesse E, Baranger L, Dautel M, Foussard C, Boasson M et al. Deregulated expression of the TAL1 gene by t(1;5)(p32;q31) in patient with T-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer 1998; 23: 36–43.

    Article  CAS  PubMed  Google Scholar 

  9. Breit TM, Mol EJ, Wolvers-Tettero IL, Ludwig WD, van Wering ER, van Dongen JJ . Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes. J Exp Med 1993; 177: 965–977.

    Article  CAS  PubMed  Google Scholar 

  10. Bernard OA, Busson-LeConiat M, Ballerini P, Mauchauffe M, Della Valle V, Monni R et al. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia 2001; 15: 1495–1504.

    Article  CAS  PubMed  Google Scholar 

  11. Helias C, Leymarie V, Entz-Werle N, Falkenrodt A, Eyer D, Costa JA et al. Translocation t(5;14)(q35;q32) in three cases of childhood T cell acute lymphoblastic leukemia: a new recurring and cryptic abnormality. Leukemia 2002; 16: 7–12.

    Article  CAS  PubMed  Google Scholar 

  12. Hayette S, Tigaud I, Maguer-Satta V, Bartholin L, Thomas X, Charrin C et al. Recurrent involvement of the MLL gene in adult T-lineage acute lymphoblastic leukemia. Blood 2002; 99: 4647–4649.

    Article  CAS  PubMed  Google Scholar 

  13. Moorman AV, Richards S, Harrison CJ . Involvement of the MLL gene in T-lineage acute lymphoblastic leukemia. Blood 2002; 100: 2273–2274.

    Article  CAS  PubMed  Google Scholar 

  14. Crist WM, Carroll AJ, Shuster JJ, Behm FG, Whitehead M, Vietti TJ et al. Poor prognosis of children with pre-B acute lymphoblastic leukemia is associated with the t(1;19)(q23;p13): a Pediatric Oncology Group study. Blood 1990; 76: 117–122.

    CAS  PubMed  Google Scholar 

  15. Uckun FM, Sensel MG, Sather HN, Gaynon PS, Arthur DC, Lange BJ et al. Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group. J Clin Oncol 1998; 16: 527–535.

    Article  CAS  PubMed  Google Scholar 

  16. Foa R, Vitale A, Mancini M, Cuneo A, Mecucci C, Elia L et al. E2A-PBX1 fusion in adult acute lymphoblastic leukaemia: biological and clinical features. Br J Haematol 2003; 120: 484–487.

    Article  CAS  PubMed  Google Scholar 

  17. Bash RO, Crist WM, Shuster JJ, Link MP, Amylon M, Pullen J et al. Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study. Blood 1993; 81: 2110–2117.

    CAS  PubMed  Google Scholar 

  18. Kikuchi A, Hayashi Y, Kobayashi S, Hanada R, Moriwaki K, Yamamoto K et al. Clinical significance of TAL1 gene alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma. Leukemia 1993; 7: 933–938.

    CAS  PubMed  Google Scholar 

  19. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002; 1: 75–87.

    Article  CAS  PubMed  Google Scholar 

  20. Ballerini P, Blaise A, Busson-Le Coniat M, Su XY, Zucman-Rossi J et al. HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis. Blood 2002; 100: 991–997.

    Article  CAS  PubMed  Google Scholar 

  21. Harrison CJ . The management of patients with leukaemia: the role of cytogenetics in this molecular era. Br J Haematol 2000; 108: 19–30.

    Article  CAS  PubMed  Google Scholar 

  22. Lo Coco F, Mandelli F, Breccia M, Annino L, Guglielmi C, Petti MC et al. Southern blot analysis of ALL-1 rearrangements at chromosome 11q23 in acute leukemia. Cancer Res 1993; 53: 3800–3803.

    CAS  PubMed  Google Scholar 

  23. Mathew S, Behm F, Dalton J, Raimondi S . Comparison of cytogenetics, Southern blotting, and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in children with acute leukemia and with 11q23 abnormalities. Leukemia 1999; 13: 1713–1720.

    Article  CAS  PubMed  Google Scholar 

  24. Rubnitz JE, Downing JR, Pui CH, Shurtleff SA, Raimondi SC, Evans WE et al. TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol 1997; 15: 1150–1157.

    Article  CAS  PubMed  Google Scholar 

  25. Pongers-Willemse MJ, Seriu T, Stolz F, d'Aniello E, Gameiro P, Pisa P et al. Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets: report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia. Leukemia 1999; 13: 110–118.

    Article  CAS  PubMed  Google Scholar 

  26. Breit TM, Beishuizen A, Ludwig WD, Mol EJ, Adriaansen HJ, van Wering ER et al. tal-1 deletions in T-cell acute lymphoblastic leukemia as PCR target for detection of minimal residual disease. Leukemia 1993; 7: 2004–2011.

    CAS  PubMed  Google Scholar 

  27. Wiemels JL, Leonard BC, Wang Y, Segal MR, Hunger SP, Smith MT et al. Site-specific translocation and evidence of postnatal origin of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2002; 99: 15101–15106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wiemels JL, Alexander FE, Cazzaniga G, Biondi A, Mayer SP, Greaves M . Microclustering of TEL-AML1 translocation breakpoints in childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 2000; 29: 219–228.

    Article  CAS  PubMed  Google Scholar 

  29. van Dongen JJM, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003; 17: 2257–2317.

    Article  CAS  PubMed  Google Scholar 

  30. van Dongen JJM, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G et al. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia 1999; 13: 1901–1928.

    Article  CAS  PubMed  Google Scholar 

  31. Szczepanski T, Orfao A, van der Velden VH, San Miguel JF, van Dongen JJ . Minimal residual disease in leukaemia patients. Lancet Oncol 2001; 2: 409–417.

    Article  CAS  PubMed  Google Scholar 

  32. Gabert J, Beillard E, Van Der Velden VH, Bi W, Grimwade D, Pallisgaard N et al. Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program. Leukemia 2003; 17: 2318–2357.

    Article  CAS  PubMed  Google Scholar 

  33. Kearney L . The impact of the new FISH technologies on the cytogenetics of haematological malignancies. Br J Haematol 1999; 104: 648–658.

    Article  CAS  PubMed  Google Scholar 

  34. van der Burg M, Smit B, Brinkhof B, Barendregt BH, Verschuren MCM, Dib M et al. A single split-signal FISH probe set allows detection of TAL1 translocations as well as SIL-TAL1 fusion genes in a single test. Leukemia 2002; 16: 755–761.

    Article  CAS  PubMed  Google Scholar 

  35. van der Burg M, Beverloo HB, Langerak AW, Wijsman J, van Drunen E, Slater R et al. Rapid and sensitive detection of all types of MLL gene translocations with a single FISH probe set. Leukemia 1999; 13: 2107–2113.

    Article  CAS  PubMed  Google Scholar 

  36. van Dongen JJM, Langerak AW . Molecular detection of chromosome aberrations (Split-signal FISH probe tchnology). International Patent 1998, PCT/NL98/00270.

  37. Megonigal MD, Rappaport EF, Jones DH, Kim CS, Nowell PC, Lange BJ et al. Panhandle PCR strategy to amplify MLL genomic breakpoints in treatment-related leukemias. Proc Natl Acad Sci USA 1997; 94: 11583–11588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Felix CA, Jones DH . Panhandle PCR: a technical advance to amplify MLL genomic translocation breakpoints. Leukemia 1998; 12: 976–981.

    Article  CAS  PubMed  Google Scholar 

  39. Britten RJ, Kohne DE . Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science 1968; 161: 529–540.

    Article  CAS  PubMed  Google Scholar 

  40. Brosius J . Retroposons-seeds of evolution. Science 1991; 251: 753.

    Article  CAS  PubMed  Google Scholar 

  41. Novick GE, Batzer MA, Deiniger PL, Herrera RJ . The mobile genetic element Alu in the human genome. Bioscience 1996; 46: 32–41.

    Article  Google Scholar 

  42. Singer MF . SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes. Cell 1982; 28: 433–434.

    Article  CAS  PubMed  Google Scholar 

  43. Korenberg JR, Rykowski MC . Human genome organization: Alu, lines, and the molecular structure of metaphase chromosome bands. Cell 1988; 53: 391–400.

    Article  CAS  PubMed  Google Scholar 

  44. Landegent JE, Jansen in de Wal N, Dirks RW, Baao F, van der Ploeg M . Use of whole cosmid cloned genomic sequences for chromosomal localization by non-radioactive in situ hybridization. Hum Genet 1987; 77: 366–370.

    Article  CAS  PubMed  Google Scholar 

  45. Nielsen PE, Egholm M, Berg RH, Buchardt O . Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 1991; 254: 1497–1500.

    Article  CAS  PubMed  Google Scholar 

  46. Egholm M, Buchardt O, Christensen L, Behrens C, Freier SM, Driver DA et al. PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules. Nature 1993; 365: 566–568.

    Article  CAS  PubMed  Google Scholar 

  47. Nielsen KV, Müller S, Poulsen TS, Gabs S, Schonau A . Combined use of PHA and DNA for fluorescence in situ hybridization (FISH). In: Nielsen PE (ed). Peptide Nuclei Acid, Protocols and Applications, 2nd edn. Wymondham: Horizon Scientific Press, 2003, pp 227–260.

    Google Scholar 

  48. van Dongen JJM, Vang Nielsen K, Pluzek KJ, Adelhorst K . Method and probes for the detection of chromosome aberrations (FISH probe/PNA based technology). International Patent 1999, PCT/DK99/00245.

  49. Murre C, McCaw PS, Baltimore D . A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 1989; 56: 777–783.

    Article  CAS  PubMed  Google Scholar 

  50. Shikano T, Kaneko Y, Takazawa M, Ueno N, Ohkawa M, Fujimoto T . Balanced and unbalanced 1;19 translocation-associated acute lymphoblastic leukemias. Cancer 1986; 58: 2239–2243.

    Article  CAS  PubMed  Google Scholar 

  51. Pui CH, Raimondi SC, Hancock ML, Rivera GK, Ribeiro RC, Mahmoud HH et al. Immunologic, cytogenetic, and clinical characterization of childhood acute lymphoblastic leukemia with the t(1;19) (q23; p13) or its derivative. J Clin Oncol 1994; 12: 2601–2606.

    Article  CAS  PubMed  Google Scholar 

  52. Secker-Walker LM, Berger R, Fenaux P, Lai JL, Nelken B, Garson M et al. Prognostic significance of the balanced t(1;19) and unbalanced der(19)t(1;19) translocations in acute lymphoblastic leukemia. Leukemia 1992; 6: 363–369.

    CAS  PubMed  Google Scholar 

  53. Mellentin JD, Murre C, Donlon TA, McCaw PS, Smith SD, Carroll AJ et al. The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias. Science 1989; 246: 379–382.

    Article  CAS  PubMed  Google Scholar 

  54. Mellentin JD, Nourse J, Hunger SP, Smith SD, Cleary ML . Molecular analysis of the t(1;19) breakpoint cluster region in pre-B cell acute lymphoblastic leukemias. Genes Chromosomes Cancer 1990; 2: 239–247.

    Article  CAS  PubMed  Google Scholar 

  55. Nourse J, Mellentin JD, Galili N, Wilkinson J, Stanbridge E, Smith SD et al. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 1990; 60: 535–545.

    Article  CAS  PubMed  Google Scholar 

  56. Boomer T, Varella-Garcia M, McGavran L, Meltesen L, Olsen AS, Hunger SP . Detection of E2A translocations in leukemias via fluorescence in situ hybridization. Leukemia 2001; 15: 95–102.

    Article  CAS  PubMed  Google Scholar 

  57. Aspland SE, Bendall HH, Murre C . The role of E2A-PBX1 in leukemogenesis. Oncogene 2001; 20: 5708–5717.

    Article  CAS  PubMed  Google Scholar 

  58. Herblot S, Aplan PD, Hoang T . Gradient of E2A activity in B-cell development. Mol Cell Biol 2002; 22: 886–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hunger SP, Ohyashiki K, Toyama K, Cleary ML . Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. Genes Dev 1992; 6: 1608–1620.

    Article  CAS  PubMed  Google Scholar 

  60. Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD et al. Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. Science 1992; 257: 531–534.

    Article  CAS  PubMed  Google Scholar 

  61. Seidel MG, Look AT . E2A-HLF usurps control of evolutionarily conserved survival pathways. Oncogene 2001; 20: 5718–5725.

    Article  CAS  PubMed  Google Scholar 

  62. Brambillasca F, Mosna G, Colombo M, Rivolta A, Caslini C, Minuzzo M et al. Identification of a novel molecular partner of the E2A gene in childhood leukemia. Leukemia 1999; 13: 369–375.

    Article  CAS  PubMed  Google Scholar 

  63. Kamps MP, Murre C, Sun XH, Baltimore D . A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell 1990; 60: 547–555.

    Article  CAS  PubMed  Google Scholar 

  64. Pui CH, Kane JR, Crist WM . Biology and treatment of infant leukemias. Leukemia 1995; 9: 762–769.

    CAS  PubMed  Google Scholar 

  65. Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa III R, Patel Y, Harden A et al. 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  PubMed  PubMed Central  Google Scholar 

  66. Ludwig WD, Rieder H, Bartram CR, Heinze B, Schwartz S, Gassmann W et al. Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89. Blood 1998; 92: 1898–1909.

    CAS  PubMed  Google Scholar 

  67. Pui CH, Chessells JM, Camitta B, Baruchel A, Biondi A, Boyett JM et al. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia 2003; 17: 700–706.

    Article  CAS  PubMed  Google Scholar 

  68. Super HJ, McCabe NR, Thirman MJ, Larson RA, Le Beau MM, Pedersen-Bjergaard J et al. Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA- topoisomerase II. Blood 1993; 82: 3705–3711.

    CAS  PubMed  Google Scholar 

  69. Andersen MK, Christiansen DH, Jensen BA, Ernst P, Hauge G, Pedersen-Bjergaard J . Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992. Br J Haematol 2001; 114: 539–543.

    Article  CAS  PubMed  Google Scholar 

  70. Harrison CJ, Cuneo A, Clark R, Johansson B, Lafage-Pochitaloff M, Mugneret F et al. Ten novel 11q23 chromosomal partner sites. Leukemia 1998; 12: 811–822.

    Article  CAS  PubMed  Google Scholar 

  71. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S et al. Hematologic malignancies with t(4;11)(q21;q23) – a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants. Leukemia 1998; 12: 779–787.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  73. Moorman AV, Hagemeijer A, Charrin C, Rieder H, Secker-Walker LM . The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. European 11q23 Workshop participants. Leukemia 1998; 12: 805–810.

    Article  CAS  PubMed  Google Scholar 

  74. Swansbury GJ, Slater R, Bain BJ, Moorman AV, Secker-Walker LM . Hematological malignancies with t(9;11)(p21-22;q23) – a laboratory and clinical study of 125 cases. European 11q23 Workshop participants. Leukemia 1998; 12: 792–800.

    Article  CAS  PubMed  Google Scholar 

  75. Lillington DM, Young BD, Berger R, Martineau M, Moorman AV, Secker-Walker LM . The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants. Leukemia 1998; 12: 801–804.

    Article  CAS  PubMed  Google Scholar 

  76. Martineau M, Berger R, Lillington DM, Moorman AV, Secker-Walker LM . The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical study of 30 cases. EU Concerted Action 11q23 Workshop participants. Leukemia 1998; 12: 788–791.

    Article  CAS  PubMed  Google Scholar 

  77. 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  PubMed  Google Scholar 

  78. Zeleznik-Le NJ, Harden AM, Rowley JD . 11q23 translocations split the ‘AT-hook’ cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci USA 1994; 91: 10610–10614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Fidanza V, Melotti P, Yano T, Nakamura T, Bradley A, Canaani E et al. Double knockout of the ALL-1 gene blocks hematopoietic differentiation in vitro. Cancer Res 1996; 56: 1179–1183.

    CAS  PubMed  Google Scholar 

  80. Kobayashi H, Espinosa R, Thirman MJ, Gill HJ, Fernaold AA, Diaz MO et al. Heterogeneity of breakpoints of 11q23 rearrangements in hematologic malignancies identified with fluorescence in situ hybridisation. Blood 1993; 82: 547–551.

    CAS  PubMed  Google Scholar 

  81. Johansson B, Moorman AV, Secker-Walker LM . Derivative chromosomes of 11q23 translocations in hematologic malignancies. Leukemia 1998; 12: 828–833.

    Article  CAS  PubMed  Google Scholar 

  82. Ayton PM, Cleary ML . Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 2001; 20: 5695–5707.

    Article  CAS  PubMed  Google Scholar 

  83. Nilson I, Lochner K, Siegler G, Greil J, Beck JD, Fey GH et al. Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias. Br J Haematol 1996; 93: 966–972.

    Article  CAS  PubMed  Google Scholar 

  84. von Bergh A, Emanuel B, van Zelderen-Bhola S, Smetsers T, van Soest R, Stul M et al. A DNA probe combination for improved detection of MLL/11q23 breakpoints by double-color interphase-FISH in acute leukemias. Genes Chromosomes Cancer 2000; 28: 14–22.

    Article  CAS  PubMed  Google Scholar 

  85. Beverloo HB, Le Coniat M, Wijsman J, Lillington DM, Bernard O, de Klein A et al. 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 

  86. Golub TR, McLean T, Stegmaier K, Carroll M, Tomasson M, Gilliland DG . The TEL gene and human leukemia. Biochim Biophys Acta 1996; 1288: M7–M10.

    PubMed  Google Scholar 

  87. Rubnitz JE, Pui CH, Downing JR . The role of TEL fusion genes in pediatric leukemias. Leukemia 1999; 13: 6–13.

    Article  CAS  PubMed  Google Scholar 

  88. Baens M, Peeters P, Guo C, Aerssens J, Marynen P . Genomic organization of TEL: the human ETS-variant gene 6. Genome Res 1996; 6: 404–413.

    Article  CAS  PubMed  Google Scholar 

  89. Wlodarska I, La Starza R, Baens M, Dierlamm J, Uyttebroeck A, Selleslag D et al. Fluorescence in situ hybridization characterization of new translocations involving TEL (ETV6) in a wide spectrum of hematologic malignancies. Blood 1998; 91: 1399–1406.

    CAS  PubMed  Google Scholar 

  90. Seeger K, von Stackelberg A, Taube T, Buchwald D, Korner G, Suttorp M et al. Relapse of TEL-AML1 – positive acute lymphoblastic leukemia in childhood: a matched-pair analysis. J Clin Oncol 2001; 19: 3188–3193.

    Article  CAS  PubMed  Google Scholar 

  91. Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML et al. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 1995; 9: 1985–1989.

    CAS  PubMed  Google Scholar 

  92. Romana SP, Poirel H, Leconiat M, Flexor MA, Mauchauffe M, Jonveaux P et al. High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia. Blood 1995; 86: 4263–4269.

    CAS  PubMed  Google Scholar 

  93. Raynaud SD, Dastugue N, Zoccola D, Shurtleff SA, Mathew S, Raimondi SC . Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia. Leukemia 1999; 13: 1325–1330.

    Article  CAS  PubMed  Google Scholar 

  94. Raynaud S, Cave H, Baens M, Bastard C, Cacheux V, Grosgeorge J et al. The 12;21 translocation involving TEL and deletion of the other TEL allele: two frequently associated alterations found in childhood acute lymphoblastic leukemia. Blood 1996; 87: 2891–2899.

    CAS  PubMed  Google Scholar 

  95. Cave H, Cacheux V, Raynaud S, Brunie G, Bakkus M, Cochaux P et al. ETV6 is the target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia. Leukemia 1997; 11: 1459–1564.

    Article  CAS  PubMed  Google Scholar 

  96. Patel N, Goff LK, Clark T, Ford AM, Foot N, Lillington D et al. Expression profile of wild-type ETV6 in childhood acute leukaemia. Br J Haematol 2003; 122: 94–98.

    Article  CAS  PubMed  Google Scholar 

  97. Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM . The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164–172.

    Article  CAS  PubMed  Google Scholar 

  98. Onida F, Ball G, Kantarjian HM, Smith TL, Glassman A, Albitar M et al. Characteristics and outcome of patients with Philadelphia chromosome negative, bcr/abl negative chronic myelogenous leukemia. Cancer 2002; 95: 1673–1684.

    Article  PubMed  Google Scholar 

  99. Wong S, Witte ON . Modeling Philadelphia chromosome positive leukemias. Oncogene 2001; 20: 5644–5659.

    Article  CAS  PubMed  Google Scholar 

  100. Arico M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 2000; 342: 998–1006.

    Article  CAS  PubMed  Google Scholar 

  101. Diekmann D, Brill S, Garrett MD, Totty N, Hsuan J, Monfries C et al. Bcr encodes a GTPase-activating protein for p21rac. Nature 1991; 351: 400–402.

    Article  CAS  PubMed  Google Scholar 

  102. Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton SW et al. Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation. Genomics 1995; 27: 67–82.

    Article  CAS  PubMed  Google Scholar 

  103. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G . Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984; 36: 93–99.

    Article  CAS  PubMed  Google Scholar 

  104. Shtivelman E, Lifshitz B, Gale RP, Canaani E . Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985; 315: 550–554.

    Article  CAS  PubMed  Google Scholar 

  105. Clark SS, McLaughlin J, Timmons M, Pendergast AM, Ben-Neriah Y, Dow LW et al. Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL). Science 1988; 239: 775–777.

    Article  CAS  PubMed  Google Scholar 

  106. Clark SS, McLaughlin J, Crist WM, Champlin R, Witte ON . Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL. Science 1987; 235: 85–88.

    Article  CAS  PubMed  Google Scholar 

  107. Selleri L, von Lindern M, Hermans A, Meijer D, Torelli G, Grosveld G . Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript. Blood 1990; 75: 1146–1153.

    CAS  PubMed  Google Scholar 

  108. Melo JV, Myint H, Galton DA, Goldman JM . P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia? Leukemia 1994; 8: 208–211.

    CAS  PubMed  Google Scholar 

  109. Pane F, Frigeri F, Sindona M, Luciano L, Ferrara F, Cimino R et al. Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction). Blood 1996; 88: 2410–2414.

    CAS  PubMed  Google Scholar 

  110. Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 2000; 95: 738–743.

    CAS  PubMed  Google Scholar 

  111. de la Fuente J, Merx K, Steer EJ, Muller M, Szydlo RM, Maywald O, Berger U, Hehlmann R, Goldman JM, Cross NC, Melo JV, Hochlaus A . ABL-BCR expression does not correlate with deletions on the derivative chromosome 9 or survival in chronic myeloid leukemia. Blood 2001; 98: 2879–2880.

    Article  CAS  PubMed  Google Scholar 

  112. Huntly BJ, Guilhot F, Reid AG, Vassiliou G, Hennig E, Franke C et al. Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions. Blood 2003; 102: 2205–2212.

    Article  CAS  PubMed  Google Scholar 

  113. Delabesse E, Bernard M, Meyer V, Smit L, Pulford K, Cayuela JM et al. TAL1 expression does not occur in the majority of T-ALL blasts. Br J Haematol 1998; 102: 449–457.

    Article  CAS  PubMed  Google Scholar 

  114. Bash RO, Hall S, Timmons CF, Crist WM, Amylon M, Smith RG et al. Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study. Blood 1995; 86: 666–676.

    CAS  PubMed  Google Scholar 

  115. Shivdasani RA, Mayer EL, Orkin SH . Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature 1995; 373: 432–434.

    Article  CAS  PubMed  Google Scholar 

  116. Porcher C, Swat W, Rockwell K, Fujiwara Y, Alt FW, Orkin SH . The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 1996; 86: 47–57.

    Article  CAS  PubMed  Google Scholar 

  117. Robb L, Elwood NJ, Elefanty AG, Kontgen F, Li R, Barnett LD et al. The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse. EMBO J 1996; 15: 4123–4129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Baer R . TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia. Semin Cancer Biol 1993; 4: 341–347.

    CAS  PubMed  Google Scholar 

  119. Aplan PD, Lombardi DP, Ginsberg AM, Cossman J, Bertness VL, Kirsch IR . Disruption of the human SCL locus by ‘illegitimate’ V-(D)-J recombinase activity. Science 1990; 250: 1426–1429.

    Article  CAS  PubMed  Google Scholar 

  120. Bernard O, Lecointe N, Jonveaux P, Souyri M, Mauchauffe M, Berger R et al. Two site-specific deletions and t(1;14) translocation restricted to human T-cell acute leukemias disrupt the 5' part of the tal-1 gene. Oncogene 1991; 6: 1477–1488.

    CAS  PubMed  Google Scholar 

  121. Delabesse E, Bernard M, Landman-Parker J, Davi F, Leboeuf D, Varet B et al. Simultaneous SIL-TAL1 RT-PCR detection of all tal(d) deletions and identification of novel tal(d) variants. Br J Haematol 1997; 99: 901–907.

    Article  CAS  PubMed  Google Scholar 

  122. Szczepanski T, Langerak AW, Wolvers-Tettero IL, Ossenkoppele GJ, Verhoef G, Stul M et al. Immunoglobulin and T cell receptor gene rearrangement patterns in acute lymphoblastic leukemia are less mature in adults than in children: implications for selection of PCR targets for detection of minimal residual disease. Leukemia 1998; 12: 1081–1088.

    Article  CAS  PubMed  Google Scholar 

  123. Aplan PD, Lombardi DP, Kirsch IR . Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia. Mol Cell Biol 1991; 11: 5462–5469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Aplan PD, Lombardi DP, Reaman GH, Sather HN, Hammond GD, Kirsch IR . Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia. Blood 1992; 79: 1327–1333.

    CAS  PubMed  Google Scholar 

  125. Brown L, Cheng JT, Chen Q, Siciliano MJ, Crist W, Buchanan G et al. Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia. EMBO J 1990; 9: 3343–3351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Bernard O, Guglielmi P, Jonveaux P, Cherif D, Gisselbrecht S, Mauchauffe M et al. Two distinct mechanisms for the SCL gene activation in the t(1;14) translocation of T-cell leukemias. Genes Chromosomes Cancer 1990; 1: 194–208.

    Article  CAS  PubMed  Google Scholar 

  127. Aplan PD, Johnson BE, Russell E, Chervinsky DS, Kirsch IR . Cloning and characterization of TCTA, a gene located at the site of a t(1;3) translocation. Cancer Res 1995; 55: 1917–1921.

    CAS  PubMed  Google Scholar 

  128. Cave H, Suciu S, Preudhomme C, Poppe B, Robert A, Uyttebroeck A et al. Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951. Blood 2003; 22: 22.

    Google Scholar 

  129. Gottgens B, Gilbert JG, Barton LM, Grafham D, Rogers J, Bentley DR et al. Long-range comparison of human and mouse SCL loci: localized regions of sensitivity to restriction endonucleases correspond precisely with peaks of conserved noncoding sequences. Genome Res 2001; 11: 87–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Mauvieux L, Leymarie V, Helias C, Perrusson N, Falkenrodt A, Lioure B et al. High incidence of Hox11L2 expression in children with T-ALL. Leukemia 2002; 16: 2417–2422.

    Article  CAS  PubMed  Google Scholar 

  131. Dear TN, Sanchez-Garcia I, Rabbitts TH . The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes. Proc Natl Acad Sci USA 1993; 90: 4431–4435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Hansen-Hagge TE, Schafer M, Kiyoi H, Morris SW, Whitlock JA, Koch P et al. Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11). Leukemia 2002; 16: 2205–2212.

    Article  CAS  PubMed  Google Scholar 

  133. Koch P, Bohlmann I, Schafer M, Hansen-Hagge TE, Kiyoi H, Wilda M et al. Identification of a novel putative Ran-binding protein and its close homologue. Biochem Biophys Res Commun 2000; 278: 241–249.

    Article  CAS  PubMed  Google Scholar 

  134. Cinti R, Fava M, Sancandi M, Matera I, Ravazzolo R, Ceccherini I . Assignment of the HOX11L2 gene to human chromosome band 5q35.1 and of its murine homolog to mouse chromosome bands 11A4-A5 by in situ hybridization. Cytogenet Cell Genet 2001; 92: 354–355.

    Article  CAS  PubMed  Google Scholar 

  135. de Boer CJ, Vaandrager JW, van Krieken JH, Holmes Z, Kluin PM, Schuuring E . Visualization of mono-allelic chromosomal aberrations 3′ and 5′ of the cyclin D1 gene in mantle cell lymphoma using DNA fiber fluorescence in situ hybridization. Oncogene 1997; 15: 1599–1603.

    Article  CAS  PubMed  Google Scholar 

  136. Vaandrager JW, Schuuring E, Philippo K, Kluin PM . V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in follicular lymphoma. Blood 2000; 96: 1947–1952.

    CAS  PubMed  Google Scholar 

  137. Poulsen TS, Silahtaroglu AN, Gisselo CG, Gaarsdal E, Rasmussen T, Tommerup N et al. Detection of illegitimate rearrangement within the immunoglobulin locus on 14q32.3 in B-cell malignancies using end-sequenced probes. Genes Chromosomes Cancer 2001; 32: 265–274.

    Article  CAS  PubMed  Google Scholar 

  138. Poulsen TS, Silahtaroglu AN, Gisselo CG, Tommerup N, Johnsen HE, Gaarsdal E et al. Detection of illegitimate rearrangements within the immunoglobulin light chain loci in B cell malignancies using end sequenced probes Detection of illegitimate rearrangement within the immunoglobulin locus on 14q32.3 in B-cell malignancies using end-sequenced probes. Leukemia 2002; 16: 2148–2155.

    Article  CAS  PubMed  Google Scholar 

  139. Gesk S, Martin-Subero JI, Harder L, Luhmann B, Schlegelberger B, Calasanz MJ et al. Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. Leukemia 2003; 17: 738–745.

    Article  CAS  PubMed  Google Scholar 

  140. Jansen MJWC, Van der Velden VHJ, Den Boer ML, Pieters R, Van Dongen JJM . Immunobiological diversity in infant acute lymphoblastic leukemia. Blood 2003; 102: 21a.

    Google Scholar 

  141. Dimartino JF, Cleary ML . Mll rearrangements in haematological malignancies: lessons from clinical and biological studies. Br J Haematol 1999; 106: 614–626.

    Article  CAS  PubMed  Google Scholar 

  142. Schoch C, Schnittger S, Klaus M, Kern W, Hiddemann W, Haferlach T . AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 2003; 102: 2395–2402.

    Article  CAS  PubMed  Google Scholar 

  143. Huret JL . 11q23 rearrangements in leukaemia. Atlas Genet Cytogenet Oncol Haematol 2003. http://www.infobiogen.fr/services/chromcancer/Anomalies/11q23ID1030.html.

  144. Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P et al. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci USA 1995; 92: 4917–4921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Romana SP, Mauchauffe M, Le Coniat M, Chumakov I, Le Paslier D, Berger R et al. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood 1995; 85: 3662–3670.

    CAS  PubMed  Google Scholar 

  146. Golub TR, Barker GF, Lovett M, Gilliland DG . Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994; 77: 307–316.

    Article  CAS  PubMed  Google Scholar 

  147. Papadopoulos P, Ridge SA, Boucher CA, Stocking C, Wiedemann LM et al. The novel activation of ABL by fusion to an ets-related gene, TEL. Cancer Res 1995; 55: 34–38.

    CAS  PubMed  Google Scholar 

  148. Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P et al. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997; 90: 2535–2540.

    CAS  PubMed  Google Scholar 

  149. Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A et al. Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11. Oncogene 1995; 10: 1511–1519.

    CAS  PubMed  Google Scholar 

  150. Raynaud SD, Baens M, Grosgeorge J, Rodgers K, Reid CD, Dainton M et al. Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes. Blood 1996; 88: 682–689.

    CAS  PubMed  Google Scholar 

  151. Voutsadakis IA, Maillard N . Acute myelogenous leukemia with the t(3;12)(q26;p13) translocation: case report and review of the literature. Am J Hematol 2003; 72: 135–137.

    Article  PubMed  Google Scholar 

  152. Cools J, Bilhou-Nabera C, Wlodarska I, Cabrol C, Talmant P, Bernard P et al. Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13). Blood 1999; 94: 1820–1824.

    CAS  PubMed  Google Scholar 

  153. Cazzaniga G, Tosi S, Aloisi A, Giudici G, Daniotti M, Pioltelli P et al. The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. Blood 1999; 94: 4370–4373.

    CAS  PubMed  Google Scholar 

  154. Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y et al. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood 1999; 93: 1355–1363.

    CAS  PubMed  Google Scholar 

  155. Chase A, Reiter A, Burci L, Cazzaniga G, Biondi A, Pickard J et al. Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia with the t(12;13)(p13;q12). Blood 1999; 93: 1025–1031.

    CAS  PubMed  Google Scholar 

  156. Qiao Y, Ogawa S, Hangaishi A, Yuji K, Izutsu K, Kunisato A et al. Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis. Leukemia 2003; 17: 1112–1120.

    Article  CAS  PubMed  Google Scholar 

  157. Kuno Y, Abe A, Emi N, Iida M, Yokozawa T, Towatari M et al. Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12). Blood 2001; 97: 1050–1055.

    Article  CAS  PubMed  Google Scholar 

  158. Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E et al. The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case. Cancer Res 2001; 61: 4666–4670.

    CAS  PubMed  Google Scholar 

  159. Strehl S, Konig M, Dworzak MN, Kalwak K, Haas OA et al. PAX5/ETV6 fusion defines cytogenetic entity dic(9;12)(p13;p13). Leukemia 2003; 17: 1121–1123.

    Article  CAS  PubMed  Google Scholar 

  160. Penas EM, Cools J, Algenstaedt P, Hinz K, Seeger D, Schafhausen P et al. A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene. Genes Chromosomes Cancer 2003; 37: 79–83.

    Article  CAS  Google Scholar 

  161. Salomon-Nguyen F, Della-Valle V, Mauchauffe M, Busson-Le Coniat M, Ghysdael J, Berger R et al. The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion. Proc Natl Acad Sci USA 2000; 97: 6757–6762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. van Rhee F, Hochhaus A, Lin F, Melo JV, Goldman JM, Cross NC . p190 BCR-ABL mRNA is expressed at low levels in p210-positive chronic myeloid and acute lymphoblastic leukemias. Blood 1996; 87: 5213–5217.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Mr T van Os for preparation of the figures and Mrs ILM Wolvers-Tettero, Mrs BH Barendregt and Mr B Brinkhof for technical assistance. We thank DakoCytomation for excellent scientific support. We are grateful to Dr T Szczepanski for critical reviewing of the manuscript and we thank Prof R Benner (head of the department of Immunology, Erasmus MC) for continuous support.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    M van der Burg, A W Langerak & J J M van Dongen

  2. DakoCytomation Denmark A/S, Glostrup, Denmark

    T S Poulsen & K Vang-Nielsen

  3. Department of Pediatric Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL, USA

    S P Hunger

  4. Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    H B Beverloo & E M E Smit

  5. Department of Cell Biology and Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    H B Beverloo & E M E Smit

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  1. M van der Burg
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van der Burg, M., Poulsen, T., Hunger, S. et al. Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia. Leukemia 18, 895–908 (2004). https://doi.org/10.1038/sj.leu.2403340

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