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ALK fusion genes in children with atypical myeloproliferative leukemia

Leukemia volume 24, pages 1197–1200 (2010)Cite this article

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The receptor tyrosine kinase ALK has a pivotal function in various malignant diseases, and its exceptional behavior is documented by the fact that chromosomal ALK rearrangements have been described in completely different malignancies, namely inflammatory myofibroblastic tumors, anaplastic large-cell lymphomas and lung cancer of the NSCLC subtype.1, 2, 3 Recently, the expression of a particular ALK fusion protein, namely TPM4-ALK, in esophageal squamous cell carcinoma was suggested.4

ALK belongs to the insulin-receptor superfamily, and its expression is normally restricted to specific regions of the central nervous system. Chromosomal translocations fusing and activating the ALK locus foster tumor genesis by its constitutive tyrosine kinase activity. In cells with ALK fusion proteins, a number of overlapping and interconnected signaling pathways are subsequently activated, for example RAS-ERK, JAK-STAT and PI3K-AKT. Enhanced proliferation and survival through inhibition of apoptosis are key features of this ALK-mediated activation of signaling cascades.5 An involvement of ALK in myeloid malignancies, however, has not yet been reported.

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References

  1. Ma Z, Hill DA, Collins MH, Morris SW, Sumegi J, Zhou M et al. Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003; 37: 98–105.

    Article  CAS  PubMed  Google Scholar 

  2. Bullrich F, Morris SW, Hummel M, Pileri S, Stein H, Croce CM . Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas. Cancer Res 1994; 54: 2873–2877.

    CAS  PubMed  Google Scholar 

  3. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448: 561–566.

    Article  CAS  PubMed  Google Scholar 

  4. Jazii FR, Najafi Z, Malekzadeh R, Conrads TP, Ziaee AA, Abnet C et al. Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer. World J Gastroenterol 2006; 12: 7104–7112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G . The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer 2008; 8: 11–23.

    Article  CAS  PubMed  Google Scholar 

  6. Trumper L, Pfreundschuh M, Bonin FV, Daus H . Detection of the t(2;5)-associated NPM/ALK fusion cDNA in peripheral blood cells of healthy individuals. Br J Haematol 1998; 103: 1138–1144.

    Article  CAS  PubMed  Google Scholar 

  7. Voena C, Conte C, Ambrogio C, Boeri EE, Boccalatte F, Mohammed S et al. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Res 2007; 67: 4278–4286.

    Article  CAS  PubMed  Google Scholar 

  8. Li R, Morris SW . Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Med Res Rev 2008; 28: 372–412.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Thomas Jung and Jutta Schieferstein for excellent technical assistance, Dr Christine Damm-Welk for fruitful discussion regarding ALK rearrangements and all clinicians in the treating. This work was supported by parents initiative Giessen. We thank Professor Dr M Bittner, National Institutes of Health (Bethesda, MD) and Dr Rocchi Cytogenetic Unit—Sezione di Genetica, (University of Bari, Italy) for allocating the CAP and alphoid FISH probes, Pediatric Oncology Centers for providing clinical data of their patients. The EWOG-MDS network and database was instrumental in tracking patient no. 6. AB was supported by the European Community Grant LSHB-CT-2004-005276, KB was founded by the ‘Deutsche José Carreras Leukämie-Stiftung’ (SP 04/06).

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Oncogenetic Laboratory, University Hospital, Justus Liebig University Giessen, Giessen, Germany

    S Röttgers, A Teigler-Schlegel & J Harbott

  2. Clinic of Pediatric Hematology, Oncology and Clinical Immunology, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany

    M Gombert & A Borkhardt

  3. Hessian State Office of Criminal Investigation—Wiesbaden, Wiesbaden, Germany

    K Busch

  4. Department of Pathology, University Hospital, Giessen, Germany

    U Gamerdinger

  5. Department of Genetics, Friedrich-Alexander University Erlangen, Erlangen, Germany

    R Slany

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  1. S Röttgers
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Correspondence to S Röttgers.

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Röttgers, S., Gombert, M., Teigler-Schlegel, A. et al. ALK fusion genes in children with atypical myeloproliferative leukemia. Leukemia 24, 1197–1200 (2010). https://doi.org/10.1038/leu.2010.18

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