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Oncogenes, Fusion Genes and Tumor Suppressor Genes

RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation

Leukemia volume 26, pages 2384–2389 (2012)Cite this article

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Abstract

Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from chimaeric fusion genes or point mutations such as BCR-ABL1 or JAK2 V617F. We report here the cloning and functional characterization of two novel fusion genes BCR-RET and FGFR1OP-RET in chronic myelomonocytic leukemia (CMML) cases generated by two balanced translocations t(10;22)(q11;q11) and t(6;10)(q27;q11), respectively. The two RET fusion genes leading to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. The RET fusion genes seem to constitutively mimic the same signaling pathway as RAS mutations frequently involved in CMML. One patient was treated with Sorafenib, a specific inhibitor of the RET TK function, and demonstrated cytological and clinical remissions.

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Acknowledgements

We are grateful for the help provided by Association Laurette-Fugain and Association de Recherche des Maladies du Sang de l'Enfant (ARMHE). CB was supported by grants from Institut National du Cancer (INCa) and Association pour la Recherche contre le Cancer (ARC). ED, CB and CC were supported by the CITTIL (Cooperacion de investigacion transpirenaica en la terapia innovadora de la leucemia), a POCTEFA grant. We thank Françoise Pflumio, Frédéric Pont and Jean-Jacques Fournié for helpful discussions. Fresh and thawed samples from AML and CMML patients have been obtained after informed consent and stored at the HIMIP collection. According to the French law, HIMIP collection has been declared to the Ministry of Higher Education and Research (DC 2008-307 collection 1) and obtained a transfer agreement (AC 2008-129) after approbation by the ‘Comité de Protection des Personnes Sud-Ouest et Outremer II’ (ethical committee). Clinical and biological annotations of the samples have been declared to the CNIL (Comité National Informatique et Libertés ie Data processing and Liberties National Committee).

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Author notes

  1. P Ballerini, S Struski, C Cresson, C Broccardo, C Perot and E Delabesse: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Hôpital Trousseau, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France

    P Ballerini, C Deswarte, A Petit, H Lapillonne, P Pages & J Donadieu

  2. Department of Hematology, Hôpital Purpan, Toulouse, France

    S Struski, N Prade, S Dobbelstein, C Demur, V Mansat- De Mas, F Huguet, N Dastugue & E Delabesse

  3. Institut National de la Santé et de la Recherche Médicale U1037, Centre de Recherche sur le Cancer de Toulouse, Toulouse, France

    C Cresson, E-F Gautier, V Mansat- De Mas, C Broccardo & E Delabesse

  4. Department of Cytogenetics, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France

    S Toujani & C Perot

  5. Department of Hematology, CHU Bordeaux and INSERM U1035, Université Victor Segalen, Bordeaux, France

    E Lippert

  6. CHU Toulouse and Université Toulouse III Paul-Sabatier, Toulouse, France

    V Mansat- De Mas & E Delabesse

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  1. P Ballerini
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Correspondence to E Delabesse.

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Ballerini, P., Struski, S., Cresson, C. et al. RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation. Leukemia 26, 2384–2389 (2012). https://doi.org/10.1038/leu.2012.109

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  • DOI: https://doi.org/10.1038/leu.2012.109

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