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Opposite expression pattern of Src kinase Lyn in acute and chronic haematological malignancies

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Abstract

Lck/yes-related novel (Lyn) tyrosine kinase overexpression has been suggested to be important for leukaemic cell growth making it an attractive target for therapy. By contrast, Lyn deficiency was shown to be responsible for a phenotype resembling myeloproliferative neoplasm (MPN) in mice. We aimed to shed more light on Lyn's role in haematological neoplasm and systematically investigated Lyn expression in MPN, acute and chronic leukaemia subtypes (n = 236). On top, B-cell chronic lymphocytic leukaemia (B-CLL) and chronic myeloid leukaemia significantly overexpressed Lyn when compared to de novo acute lymphoblastic leukaemia, de novo acute myeloid leukaemia (AML) and Philadelphia-chromosome-negative myeloproliferative neoplasms (p < 0.001). Most of acute leukaemia subtypes showed a notable down-regulation of Lyn mRNA but anyhow individual cases were labelled for the active form of Lyn protein. Intriguingly, secondary AML evolved in myelodysplastic syndromes revealed almost undetectable Lyn. Overexpression of Lyn in B-CLL was associated with a significant down-regulation of microRNA-337-5p suggesting that aberrant expression of this particular microRNA could be involved in post-transcriptional control of Lyn mRNA fate. We conclude that tyrosine kinase Lyn contributes to the malignant phenotype in certain leukaemia subtypes and therefore attracts targeted therapy.

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Acknowledgements

The authors are indebted to Ms. Sabine Schroeter and Ms. Anna-Lena Becker for their skilled technical assistance.

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Authors and Affiliations

  1. Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Kais Hussein, Guntram Büsche, Thomas Buhr, Hans Kreipe & Oliver Bock

  2. Institute of Cellular and Molecular Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Nils von Neuhoff

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  1. Kais Hussein
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  2. Nils von Neuhoff
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  3. Guntram Büsche
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  4. Thomas Buhr
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  5. Hans Kreipe
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  6. Oliver Bock
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Corresponding author

Correspondence to Oliver Bock.

Additional information

Research grant: Deutsche Krebshilfe, Dr. Mildred Scheel Stiftung (10-2191/O.B., H.K.) and the Deutsche Forschungsgemeinschaft (DFG/Bo 1954/1-1/O.B., H.K.), Hochschul-interne Leistungsförderung—HiLF 11/07, Medizinische Hochschule Hannover (K.H.)

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Hussein, K., von Neuhoff, N., Büsche, G. et al. Opposite expression pattern of Src kinase Lyn in acute and chronic haematological malignancies. Ann Hematol 88, 1059–1067 (2009). https://doi.org/10.1007/s00277-009-0727-5

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  • DOI: https://doi.org/10.1007/s00277-009-0727-5

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