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Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia

Leukemia volume 16, pages 2055–2061 (2002)Cite this article

Abstract

Within 285 adult acute lymphoblastic leukemias (ALL) included in the multicenter GIMEMA 0496 trial and prospectively studied by conventional cytogenetics, 18 cases (6%) with long arm deletion of chromosome 6 (6q) were identified. These cases were divided into: (i) del(6q) only (n = 6); (ii) del(6q) plus other numerical and/or structural abnormalities (n = 8); (iii) del(6q) and other ‘specific’ translocations (n = 4). The biologic and clinical features of the patients carrying this anomaly, as well as their outcome, were compared with those of 267 patients without del(6q). A T cell phenotype was more frequently associated with del(6q) cases in general (P = 0.001) and particularly with cases presenting del(6q) as the isolated abnormality (P = 0.0027). No significant difference with respect to multidrug resistance (MDR)/P glycoprotein expression was observed between the two groups of patients (21% vs 28% of MDR-positive cases, respectively). A BCR-ABL fusion transcript was less frequently detected in cases with del(6q) (11%) compared with those without the anomaly (29%). p15 and p16 deletions were identified by Southern blot analysis in 21% of cases with del(6q) and in 26% of cases without del(6q). In this latter group, a T cell phenotype was less frequently associated with p15 and/or p16 deletion than in the group carrying del(6q) (36% vs 100% of cases, P = 0.011). Overall, patients with ALL and del(6q) had a high complete remission (CR) rate (83%); however, they had a lower 18 month event-free survival (31% vs 41%) and a higher relapse rate (70% vs 37%, P = 0.02) compared with patients without del(6q). To date, this is the largest series of adult ALL cases reported with del(6q) homogeneously treated, which have also been prospectively studied for MDR expression and for the detection of known fusion genes. This anomaly, as an isolated change, identifies a subset of cases with hyperleukocytosis (median WBC count 52 × 109/l) and a strict correlation with a T cell phenotype. Overall, del(6q) seems to be associated with an unfavorable clinical outcome, although this finding will need to be confirmed by extended FISH analysis.

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Acknowledgements

Work supported by Istituto Superiore di Sanità, Italy–USA program on ‘Therapy of Tumors’, Rome; Associazione Italiana per la Ricerca sul Cancro (AIRC) Milan, legge 27 dicembre 1997, No. 449, Associazione Italiana contro le Leucemie sezione di Roma (ROMAIL), Italy; MURST fondi 60%. CM is supported by AIRC and AIL. We thank Dr S Raimondi for useful advice and comments.

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Authors and Affiliations

  1. Department of Cellular Biotechnologies and Hematology, University ‘La Sapienza’, Rome, Italy

    M Mancini, ML Vegna, F Spirito, L Elia, A Tafuri, L Annino, I Della Starza, F Mandelli & R Foà

  2. Department of Biomedical Sciences, Hematology Unit, University of Ferrara, Italy

    GL Castoldi

  3. Hematology, University of Perugia, Italy

    C Mecucci

  4. Department of Biochemistry and Medical Biotechnologies, Hematology, University ‘Federico II’, Naples, Italy

    F Pane, A Camera & L Luciano

  5. Department of Clinical and Biological Sciences, University of Turin, ‘SL Gonzaga’ Hospital, Orbassano-Turin, Turin, Italy

    G Rege-Cambrin

  6. Department of Clinical and Experimental Medicine, Hematology Section, University of Verona, Italy

    M Gottardi

  7. Department of Hematology, Ancona University School of Medicine, Ancona, Italy

    P Leoni

  8. Division of Hematology, ‘S Giovanni Battista’ Hospital, Turin, Italy

    E Gallo

  9. Department of Hematology, University of Bari, Bari, Italy

    G Specchia

  10. Department of Medical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy

    G Torelli

  11. Division of Hematology, Civil Hospital, Pescara, Italy

    M Sborgia

  12. Division of Hematology, ‘S Francesco’ Hospital, Nuoro, Italy

    A Gabbas

  13. Division of Hematology, ‘Niguarda Cà Granda’ Hospital, Milan, Italy

    A Tedeschi

  14. Department of Hematology, IRCCS – ‘Casa Sollievo Della Sofferenza’ Hospital, San Giovanni Rotondo, Italy

    N Cascavilla

  15. Chair of Hematology, University of Catania, Catania, Italy

    F Di Raimondo

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  1. M Mancini
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  2. ML Vegna
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  14. A Camera
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  15. L Luciano
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  16. G Specchia
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  17. G Torelli
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  18. M Sborgia
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  19. A Gabbas
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  21. I Della Starza
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Mancini, M., Vegna, M., Castoldi, G. et al. Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia. Leukemia 16, 2055–2061 (2002). https://doi.org/10.1038/sj.leu.2402640

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  • DOI: https://doi.org/10.1038/sj.leu.2402640

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