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:

Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia

Leukemia volume 25, pages 1192–1194 (2011)Cite this article

Subjects

Chimeric fusion genes are highly prevalent in childhood acute leukemia and have been recognized as causal events in the process of leukemic transformation. Infant leukemia, for example, is characterized by the very frequent occurrence of MLL gene rearrangements. These genetic events are mostly initiated in utero as substantially evidenced by studies of twins with leukemia, retrospective analysis of neonatal blood spots and cord blood screening.1

The chromosomal translocation t(2;11)(q31;p15) results in the NUP98-HOXD13 (ND13) gene fusion which was first identified in a patient with therapy-related AML.2 Albeit rare, it is a recurrent event in de novo AML3 and has also been reported in infant AML.4, 5 In this report, we identified the third infant diagnosed with AML presenting with ND13. All three patients were diagnosed at highly similar ages, varying from 9–11 months, which might indicate a rapid onset of leukemia development. Based on the yet available information, the ND13 in infants correlates with the phenotype AML-M4 and is associated with a good prognosis. By applying state-of-the-art technologies,6 the genomic breakpoint sequence was unveiled. This allowed us to screen an archived neonatal blood spot to demonstrate for the first time the presence of a concordant ND13 gene fusion. Detailed methods performed in this study are described in Supplementary Information.

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
Figure 2

References

  1. Greaves MF, Wiemels J . Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 2003; 3: 639–649.

    Article  CAS  Google Scholar 

  2. Raza-Egilmez SZ, Jani-Sait SN, Grossi M, Higgins MJ, Shows TB, Aplan PD . NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia. Cancer Res 1998; 58: 4269–4273.

    CAS  PubMed  Google Scholar 

  3. Arai Y, Kyo T, Miwa H, Arai K, Kamada N, Kita K et al. Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation. Leukemia 2000; 14: 1621–1629.

    Article  CAS  Google Scholar 

  4. Hidaka E, Tanaka M, Matsuda K, Ishikawa-Matsumura M, Yamauchi K, Sano K et al. A complex karyotype, including a three-way translocation generating a NUP98-HOXD13 transcript, in an infant with acute myeloid leukemia. Cancer Genet Cytogenet 2007; 176: 137–143.

    Article  CAS  Google Scholar 

  5. Shimada H, Arai Y, Sekiguchi S, Ishii T, Tanitsu S, Sasaki M . Generation of the NUP98-HOXD13 fusion transcript by a rare translocation, t(2;11)(q31;p15), in a case of infant leukaemia. Br J Haematol 2000; 110: 210–213.

    Article  CAS  Google Scholar 

  6. Meyer C, Schneider B, Reichel M, Angermueller S, Strehl S, Schnittger S et al. Diagnostic tool for the identification of MLL rearrangements including unknown partner genes. Proc Natl Acad Sci USA 2005; 102: 449–454.

    Article  CAS  Google Scholar 

  7. Palmqvist L, Pineault N, Wasslavik C, Humphries RK . Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes. PLoS One 2007; 2: e768.

    Article  Google Scholar 

  8. Gale KB, Ford AM, Repp R, Borkhardt A, Keller C, Eden OB et al. Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 1997; 94: 13950–13954.

    Article  CAS  Google Scholar 

  9. Nishiyama M, Arai Y, Tsunematsu Y, Kobayashi H, Asami K, Yabe M et al. 11p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome. Genes Chromosomes Cancer 1999; 26: 215–220.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are very grateful to Caroline Barbieri for her assistance in Guthrie card collection, to Marcela Braga Mansur for helpful comments on sequencing data, and to Thayana da Conceição Barbosa for performing the analysis of additional molecular alterations. This work was supported by grants from the CAPES-PROBRAL Program #345/10 (Brazil) and DAAD #50724490 (Germany), by the INCT-Controle do Cancer; CNPq #573806/2008–0, and FAPERJ #E026/2008 and a grant from the German Cancer Aid #108400.

Author information

Authors and Affiliations

  1. Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil

    M Emerenciano & M S Pombo-de-Oliveira

  2. Institute of Pharmaceutical Biology/ZAFES/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University of Frankfurt, Frankfurt/Main, Germany

    C Meyer & R Marschalek

  3. Cytogenetics Laboratory-CEMO, Instituto Nacional de Câncer, Rio de Janeiro, Brazil

    M L Macedo-Silva

  4. Hematology Service, Hospital do Câncer I, Instituto Nacional de Câncer, Rio de Janeiro, Brazil

    E de Meis & J A Dobbin

Authors
  1. M Emerenciano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M L Macedo-Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E de Meis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J A Dobbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Marschalek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M S Pombo-de-Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M S Pombo-de-Oliveira.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Emerenciano, M., Meyer, C., Macedo-Silva, M. et al. Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia. Leukemia 25, 1192–1194 (2011). https://doi.org/10.1038/leu.2011.51

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.51

Search

Advanced search

Quick links