Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Transition from EML1-ABL1 to NUP214-ABL1 positivity in a patient with acute T-lymphoblastic leukemia

Leukemia volume 20, pages 2202–2204 (2006)Cite this article

Acute T-lymphoblastic leukemia (T-ALL) is caused by the cooperation of different classes of mutations providing deregulation of the cell cycle, impaired differentiation, stimulation of the proliferation and unlimited self-renewal capacity of the leukemic cells.1, 2 Deletion of CDKN2A (p16), overexpression of TLX1 or TLX3 and mutation of NOTCH1 are typical examples of genetic aberrations that are implicated in the pathogenesis of T-ALL.3, 4 In addition, we have recently identified NUP214-ABL1 and EML1-ABL1 as novel ABL1-fusion genes in up to 8% of T-ALLs, which are believed to provide a proliferation and survival advantage in T-ALL.5, 6, 7, 8, 9

We previously described a T-ALL patient carrying a cryptic t(9;14)(q34;q32) resulting in the generation of an imatinib sensitive EML1-ABL1 fusion gene.10 At diagnosis, this patient also overexpressed TLX1 and showed hemizygous CDKN2A deletion in the leukemic cells.10 Finally, NOTCH1 sequencing revealed a S2493*STOP mutation in the PEST domain of NOTCH1. He was treated with remission induction therapy (cyclophosphamide, vincristine, daunorubicin, asparaginase and corticosteroids), resulting in complete hematological and immunophenotypic remission 1 month later. Three consolidation courses (methotrexate; Ara-C and m-amsacrine; and mitoxantrone and VP-16) were given followed by maintenance therapy with weekly methotrexate and daily 6-thioguanine. Reverse transcription-polymerase chain reaction (RT-PCR) for EML1-ABL1, which was positive at diagnosis, was negative at month 21. Twenty-seven months after initial diagnosis, the patient relapsed hematologically, for which he was treated elsewhere.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. De Keersmaecker K, Marynen P, Cools J . Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia. Haematologica 2005; 90: 1116–1127.

    CAS  Google Scholar 

  2. Grabher C, von Boehmer H, Look AT . Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer 2006; 6: 347–359.

    Article  CAS  Google Scholar 

  3. Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R et al. Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet 2004; 36: 1084–1089.

    Article  CAS  Google Scholar 

  4. Weng AP, Ferrando AA, Lee W, Morris JP, Silverman LB, Sanchez-Irizarry C et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306: 269–271.

    Article  CAS  Google Scholar 

  5. Graux C, Cools J, Michaux L, Vandenberghe P, Hagemeijer A . Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 2006; 20: 1496–1510.

    Article  CAS  Google Scholar 

  6. De Keersmaecker K, Marynen P, Cools J . Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia. Haematologica 2005; 90: 1116–1127.

    CAS  Google Scholar 

  7. Ballerini P, Busson M, Fasola S, van den Akker J, Lapillonne H, Romana SP et al. NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance. Leukemia 2005; 19: 468–470.

    Article  CAS  Google Scholar 

  8. Burmeister T, Gokbuget N, Reinhardt R, Rieder H, Hoelzer D, Schwartz S . NUP214-ABL1 in adult T-ALL: the GMALL study group experience. Blood First Edition Paper 2006, DOI 10.1182/blood-2006-04-014514.

  9. Barber KE, Martineau M, Harewood L, Stewart M, Cameron E, Strefford JC et al. Amplification of the ABL gene in T-cell acute lymphoblastic leukemia. Leukemia 2004; 18: 1153–1156.

    Article  CAS  Google Scholar 

  10. De Keersmaecker K, Graux C, Odero MD, Mentens N, Somers R, Maertens J et al. Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32). Blood 2005; 105: 4849–4852.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Grant G.0507.04 of the ‘Fonds voor Wetenschappelijk Onderzoek Vlaanderen’; the Interuniversity Attraction Poles (IAP) granted by the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2002–2006; P5/25); a Concerted Action Grant from the KU Leuven; the Belgian Federation against Cancer (SCIE2003-19), and the European Hematology Association (Jose Carreras grant to JC). PV is a senior clinical investigator, KDK an ‘aspirant’, JC a postdoctoral researcher and IL a visiting postdoctoral researcher of the ‘Fonds voor Wetenschappelijk Onderzoek-Vlaanderen’.

Author information

Authors and Affiliations

  1. Department of Molecular and Developmental Genetics – Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium

    K De Keersmaecker, I Lahortiga, P Marynen & J Cools

  2. CIMA, University of Pamplona, Pamplona, Spain

    I Lahortiga

  3. Department of Hematology, Cliniques Universitaires StLuc, Catholic University of Louvain, Brussels, Belgium

    C Graux

  4. Department of Hematology, University of Leuven, Leuven, Belgium

    J Maertens

  5. Department of Human Genetics, University of Leuven, Leuven, Belgium

    P Vandenberghe

Authors
  1. K De Keersmaecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I Lahortiga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Graux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Marynen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Maertens
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Cools
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Vandenberghe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Vandenberghe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Keersmaecker, K., Lahortiga, I., Graux, C. et al. Transition from EML1-ABL1 to NUP214-ABL1 positivity in a patient with acute T-lymphoblastic leukemia. Leukemia 20, 2202–2204 (2006). https://doi.org/10.1038/sj.leu.2404425

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404425

This article is cited by

Search

Advanced search

Quick links