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t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH)

Abstract

To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children 15 years and 153 adults), and 67 (18.5%) [47 children (22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5;14)q35;q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression.

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References

  1. Romana SP, Mauchauffé 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  Google Scholar 

  2. Jaju RJ, Haas OA, Neat M, Harbott J, Saha V, Boultwood J et al. A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. Blood 1999; 94: 773–780.

    CAS  PubMed  Google Scholar 

  3. Bernard OA, Busson-Le Coniat M, Ballerini P, Mauchauffé 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  Google Scholar 

  4. Hélias C, Leymarie V, Entz-Werle N, Falkenrodt A, Eyer D, Aurich-Costa J et al. Translocation t(5;14)(q35;q32) in 3 cases of childhood T-cell acute lymphoblastic leukemia: a new recurring and cryptic abnormality. Leukemia 2002; 16: 7–12.

    Article  Google Scholar 

  5. Dubé ID, Kamel-Reid S, Yuan CC, Lu M, Wu X, Corpus G et al. A novel homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14). Blood 1991; 78: 2996–3003.

    PubMed  Google Scholar 

  6. Hatano M, Roberts CW, Minden M, Crist WM, Korsmeyer SJ . Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Science 1991; 253: 79–82.

    Article  CAS  Google Scholar 

  7. Vilmer E, Suciu S, Ferster A, Bertrand Y, Cavé H, Thyss A et al. Long-term results of three randomized trials (58831, 58832, 58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report. Leukemia 2000; 14: 2257–2266.

    Article  CAS  Google Scholar 

  8. Donadieu J, Auclerc MF, Baruchel A, Perel Y, Bordigoni P, Landman-Parker J et al. Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE). Br J Cancer 2000; 83: 1617–1622.

    Article  CAS  Google Scholar 

  9. Dombret H, Gabert J, Boiron J-M, Rigal-Huret F, Blaise D, Thomas X et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia – results of the prospective multicenter LALA-94 trial. Blood 2002; 100: 2057–2066.

    Article  Google Scholar 

  10. European Group for the Immunological Characterization of Leukemias. (EGIL): Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van't Veer MB . Proposals for the immunological classification of acute leukemias. Leukemia 1995; 9: 1783–1786.

    Google Scholar 

  11. ISCN 1995. An International System for Human Cytogenetic Nomenclature. In: Mitelman F (ed). Basel, Switzerland: Karger, 1995.

  12. Ballerini P, Blaise A, Busson-Le Coniat M, Su X-Y, Zucman-Rossi J, Adam M et al. Hox11L2 expression defines a clinical subtype of pediatrc T-ALL associated with poor prognostic. Blood 2002; 100: 991–997.

    Article  CAS  Google Scholar 

  13. Mauvieux L, Leymarie V, Helias C, Perusson N, Falkenrodt A, Lioure B et al. High incidence of HOX11L2 expression in children with T-ALL. Leukemia 2002; 16: 2417–2422.

    Article  CAS  Google Scholar 

  14. Whitlock JA, Raimondi SC, Harbott J, Morris SW, McCurley TL, Hansen-Hagge TE et al. t(5;14)(q33-34;q11), a new recurring cytogenetic abnormality in childhood acute leukemia. Leukemia 1994; 8: 1539–1543.

    CAS  PubMed  Google Scholar 

  15. Hansen-Haage TE, Schäfer M, Kiyoi H, Morris SW, Whitlock JA, Koch P et al. Disruption of the RanbBP17/Hox11L2 region by recombination with the TCRd locus in acute lymphoblastic leukemias with t(5;14)(q34;q11). Leukemia 2002; 16: 22205–22212.

    Google Scholar 

  16. Begley CG, Green AR . The SCL gene: from case report to critical hematopoietic regulator. Blood 1999; 93: 1760–1770.

    Google Scholar 

  17. 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 

  18. 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  Google Scholar 

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Acknowledgements

The Belgian contribution to this work presents research results of the Belgian Programme of Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. We own scientific responsibility of this work.

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Appendix

Appendix

The Appendix lists the name of the city, the name of the institute, followed by the names of other participants and the number of cases in parentheses.

Toulouse: Centre Hospitalier Universitaire Hôpital Purpan: EE Kuhlein, E Duchayne, A Robert, F Huguet (53).

Paris: Hôpital Trousseau et CHU Saint Antoine: M Adam, L Douay, J Landman-Parker, G Leverger (45).

Paris: Hôpital Saint Louis: X-Y Su, M-T Daniel (40).

Louvain: Katholieke Universiteit Leuven: A Uyttebroek, C Doyen, A Delannoy, B Deprijck; Université Catholique de Louvain: C Verellen-Dumoulin, JM Libouton, JP Scheiff, V Deneys, C Vermylen, A Bruwier, D Latinne, J-L Vaerman, A Ferrant, A Bruniez (32).

Lyon: Hôpital Edouard Herriot and Hôpital Debrousse: I Tigaud, E Callet-Bauchu, D Treille-Ritouet, X Thomas (30).

Dijon: Centre Hopitalier Universitaire: B Favre, M Maynadié, D Caillo (25).

Lille: Centre Hospitalier Universitaire: P Lepelley, C Roumieux, N Grardel (18).

Nantes: Centre Hospitalier Universitaire Hôtel-Dieu: H Hervé-Loiseau (18).

Strasbourg: Centre Hospitalier Régional Universitaire: M Lessard, V Leymarie, C Gervais (18).

Marseille: Institut Paoli-Calmettes: D Sainty, C Arnoulet, R Bouabdallah, D Coso, A Charbonnier, D Blaise, A-M Stoppa, N Vey (14).

Reims: Centre Hospitalier Universitaire: I Luquet, S Daliphard (14).

Paris: Centre Hospitalier Universitaire Necker-Enfants Malades: S Romana (12).

Bordeaux: Centre Hospitalier Universitaire Hôpital Haut Lévêque: J-P Vial, F Lacombe, J-M Boiron (11).

Paris: Hôpital Pitié-Salpétrière: H Merle-Béral, CERBA: H Mossafa (11).

Gand: Centre for Medical Genetics, Belgique: J Philippé, B Verhasselt, Y Benoit (8).

Rouen: Centre Anticancéreux Henri Becquerel: A Stamboulas, MP Callat (7).

Marseille: Hôpital Timone-Enfants: H Zattara (3).

Liège: Université de Liège, ULCB, Belgique (3).

Nancy: Centre Hospitalier Universitaire de Nancy Brabois: P Jonveaux, J Buisine, L Mansury (2).

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Berger, R., Dastugue, N., Busson, M. et al. t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH). Leukemia 17, 1851–1857 (2003). https://doi.org/10.1038/sj.leu.2403061

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