title: RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation.
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.
authors.affiliation: Department of Hematology, Hôpital Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Ballerini
authors.forename: S
authors.initials: S
authors.lastname: Struski
authors.forename: C
authors.initials: C
authors.lastname: Cresson
authors.forename: N
authors.initials: N
authors.lastname: Prade
authors.forename: S
authors.initials: S
authors.lastname: Toujani
authors.forename: C
authors.initials: C
authors.lastname: Deswarte
authors.forename: S
authors.initials: S
authors.lastname: Dobbelstein
authors.forename: A
authors.initials: A
authors.lastname: Petit
authors.forename: H
authors.initials: H
authors.lastname: Lapillonne
authors.forename: E-F
authors.initials: EF
authors.lastname: Gautier
authors.forename: C
authors.initials: C
authors.lastname: Demur
authors.forename: E
authors.initials: E
authors.lastname: Lippert
authors.forename: P
authors.initials: P
authors.lastname: Pages
authors.forename: V
authors.initials: V
authors.lastname: Mansat-De Mas
authors.forename: J
authors.initials: J
authors.lastname: Donadieu
authors.forename: F
authors.initials: F
authors.lastname: Huguet
authors.forename: N
authors.initials: N
authors.lastname: Dastugue
authors.forename: C
authors.initials: C
authors.lastname: Broccardo
authors.forename: C
authors.initials: C
authors.lastname: Perot
authors.forename: E
authors.initials: E
authors.lastname: Delabesse
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D017931:DNA Primers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000473:pathology*; D009000:Monocytes / Q000166:cytology*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human