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

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Ballerini, P | Struski, S | Cresson, C | Prade, N | Toujani, S | Deswarte, C | Dobbelstein, S | Petit, A | Lapillonne, H | Gautier, E-F | Demur, C | Lippert, E | Pages, P | Mansat-de Mas, V | Donadieu, J | Huguet, F | Dastugue, N | Broccardo, C | Perot, C | Delabesse, Eric | Mansat- de Mas, V

Edité par CCSD ; Springer Nature -

International audience. 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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