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Altered splicing in hematological malignancies reveals a tissue-specific translational block of the Src-family tyrosine kinase fyn brain isoform expression

Leukemia volume 18, pages 1737–1739 (2004)Cite this article

TO THE EDITOR

In common with other Src family-related members, the tyrosine kinase fyn has been implicated in malignant pathological processes, including melanoma progression, genesis of neuroblastoma, or carcinoma invasion.1 The expression of fyn in hematological malignancies is, however, not known. Fyn is transcribed in hematopoietic tissues and in the central nervous system (CNS). Two main isoforms, FynB and FynT, arise by alternative splicing of the fyn gene exon 7A and 7B, respectively. FynT is expressed in the hematopoietic lineage and FynB in the brain.2 In hematopoïetic tissues and in the CNS, alternative splicing of exon 7A or 7B is mutually exclusive. It would be secondary to the capture of exon 7A by the ancestral fyn gene, which was recruited by the brain while the ancestral exon 7B was conserved and expressed in the hematopoietic lineage.3 The exon 7 sequences encode for the linker region involved in intramolecular interactions controlling Src tyrosine kinase regulation.1 Ex vivo experiments showed that the two isoforms possess distinct signaling and transforming capabilities.4, 5 Hence, altered splicing of fyn messengers might contribute to altered Fyn function in specific tissues. Indeed, it was shown that fynB mRNA was strongly upregulated in a HTLV1-infected T cell line (C91).6 These data suggest that, under certain conditions, the regulation of the alternative splicing can be modulated and that the FynB isoform could be expressed in lymphocytes. However, mRNA and protein expression profiles of both isoforms have not yet been studied in detail in lymphoid cells.

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References

  1. Yeatman TJ . A renaissance for Src. Nat Rev Cancer 2004; 4: 470–480.

    Article  CAS  PubMed  Google Scholar 

  2. Cooke MP, Perlmutter RM . Expression of a novel form of the fyn proto-oncogene in hematopoietic cells. New Biol 1989; 1: 66–74.

    CAS  PubMed  Google Scholar 

  3. Picard C, Gilles A, Pontarotti P, Olive D, Collette Y . Cutting edge: recruitment of the ancestral fyn gene during emergence of the adaptive immune system. J Immunol 2002; 168: 2595–2598.

    Article  CAS  PubMed  Google Scholar 

  4. Davidson D, Chow LM, Fournel M, Veillette A . Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn. J Exp Med 1992; 175: 1483–1492.

    Article  CAS  PubMed  Google Scholar 

  5. Davidson D, Fournel M, Veillette A . Oncogenic activation of p59fyn tyrosine protein kinase by mutation of its carboxyl-terminal site of tyrosine phosphorylation, tyrosine 528. J Biol Chem 1994; 269: 10956–10963.

    CAS  PubMed  Google Scholar 

  6. Weil R, Levraud JP, Dodon MD, Bessia C, Hazan U, Kourilsky P et al. Altered expression of tyrosine kinases of the Src, Syk families in human T-cell leukemia virus type 1-infected T-cell lines. J Virol 1999; 73: 3709–3717.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Moderek B, Lee C . A genomic view of alternative splicing. Nat Genet 2002; 30: 13–19.

    Article  Google Scholar 

  8. Lee C, Kim MG, Jeon SH, Park SD, Seong RH . Two species of mRNA for the fyn proto-oncogene are produced by an alternative polyadenylation. Mol Cells 1998; 8: 746–749.

    CAS  PubMed  Google Scholar 

  9. Berwanger B, Hartmann O, Bergmann E, Bernard S, Nielsen D, Krause M et al. Loss of a FYN-regulated differentiation and growth arrest pathway in advanced stage neuroblastoma. Cancer Cell 2002; 2: 377–386.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Département de Biochimie et de Biologie Moléculaire, Hôpital Universitaire Nord, IFR Jean Roche, Université de la Méditerranée, Marseilles cedex, France

    C Picard & J Gabert

  2. Institut de Recherches sur le Cancer de Marseille, Université de la Méditerranée, Marseilles, France

    C Picard, D Olive & Y Collette

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  1. C Picard
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  2. J Gabert
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  3. D Olive
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  4. Y Collette
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Correspondence to Y Collette.

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Picard, C., Gabert, J., Olive, D. et al. Altered splicing in hematological malignancies reveals a tissue-specific translational block of the Src-family tyrosine kinase fyn brain isoform expression. Leukemia 18, 1737–1739 (2004). https://doi.org/10.1038/sj.leu.2403499

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