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NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance

Leukemia volume 19, pages 468–470 (2005)Cite this article

HOX11L2 expression, mostly resulting from the chromosomal cryptic translocation t(5;14)(q35;q32), is observed in more than 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL) and in about 13% of adult T-ALL.1,2 The prognostic significance of the genetic abnormality in patients with this subtype of ALL is still controversial, claimed as unfavorable for some groups3,4 or regarded as neutral for others.5,6 Recently, episomal amplification encompassing the ABL1 gene has been found in 2.3 and 4.3% of childhood and adult T-ALL.7 The incidence of ABL1 amplification rose to 5.8% of T-ALL by Graux et al,8 who showed that a new fusion gene, NUP214-ABL1, was included in the episomal amplicon. Moreover, the latter authors showed that the NUP214-ABL1 fusion was mainly present in T-ALL expressing HOX11 or HOX11L2. We hypothesized that the expression of the fusion gene might account for the discrepancies observed in the evolution of individual HOX11L2-positive patients with T-ALL. We report the finding of fluorescence in situ hybridization (FISH) and real-time PCR in a child with T-ALL with a peculiar form of amplification and rapidly fatal evolution.

GD, a 9-year-old boy was admitted to the hematological unit of the Armand Trousseau hospital (Paris) with a suspicion of leukemia because of fever, erythematous angina, enlarged cervical lymph nodes and hyperleukocytosis. Clinical and radiological examination displayed mediastinal enlargement, hepatosplenomegaly and voluminous mesenteric lymph nodes. Hematologic data confirmed the diagnosis of acute leukemia: in peripheral blood, 302 × 109/l leukocytes with 93% lymphoblasts, 116 × 109/l platelets and hemoglobin 117 g/l. Immunophenotyping revealed an immature T-cell leukemia scoring positive for c-CD3, CD2, CD4, CD5, CD7 and CD8 antigens. All the myeloid antigens tested (CD13, CD14, CD15, CD33, CD117, CD35 and c-MPO) were negative, with the exception of CD33. The child immediately received induction therapy including prednisolone prephase, vincristine 1.5 mg/m2 weekly × 4, cyclophosphamide 1 g/m2 day 8, asparaginase 6000 IU × 8, daunorubicin 40 mg/m2 days 8, 9, 10 and 15 and two intrathecal injections of methotrexate and aracytine. At day 7, he demonstrated corticoid resistance, and at day 21, bone marrow was aplastic with persistence of 83% leukemic cells. No remission could be obtained and the child died 30 days after the diagnosis because of massive intracranial hemorrhage.

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Authors and Affiliations

  1. Service d'Hématologie Biologique, Hôpital A Trousseau, Paris, France

    P Ballerini & H Lapillonne

  2. EMI 0210 INSERM, Hôpital Necker-Enfants Malades, Paris, France

    M Busson, S P Romana, O A Bernard & R Berger

  3. Service d'Hématologie et d'Oncologie Pédiatrique, Hôpital A Trousseau, Paris, France

    S Fasola & J Landman-Parker

  4. Service d'Embryologie Pathologique et Cytogénétique, Hôpital Saint Antoine, Paris, France

    J van den Akker

  5. Service d'Histologie-Embryologie et de Cytogénétique, Hôpital Necker-Enfants Malades, Paris, France

    S P Romana

  6. Center for Human Genetics, University of Leuven, Leuven, Belgium

    P Marynen

  7. UPRES 1638, Université Paris VI, France

    P Ballerini, H Lapillonne & J Landman-Parker

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  1. P Ballerini
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Ballerini, P., Busson, M., Fasola, S. et al. NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance. Leukemia 19, 468–470 (2005). https://doi.org/10.1038/sj.leu.2403654

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