title: Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia.
abstract: Chronic myelomonocytic leukemia (CMML) is a clonal disorder sharing features of myelodysplastic syndromes and chronic myeloproliferative neoplasms. Although rare chromosomal aberrations and point mutations are reported in CMML, the molecular defects underlying CMML are largely unknown. ROS1 encodes a tyrosine kinase that is abnormally expressed and translocated in brain and lung cancers. In this study we show that ROS1 is abnormally activated in the CD34+ compartment of approximately 70% of CMML patients resulting in the activation of the Erk/Akt pathways through the Grb2/SOS complex thus revealing a central oncogenic role for ROS1 in CMML which might represent a molecular target.
authors: Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. daniela.cilloni@unito.it
authors: Daniela
authors: D
authors: Cilloni
authors: Sonia
authors: S
authors: Carturan
authors: Enrico
authors: E
authors: Bracco
authors: Valentina
authors: V
authors: Campia
authors: Valentina
authors: V
authors: Rosso
authors: Davide
authors: D
authors: Torti
authors: Chiara
authors: C
authors: Calabrese
authors: Valentina
authors: V
authors: Gaidano
authors: Pimjai
authors: P
authors: Niparuck
authors: Alessandra
authors: A
authors: Favole
authors: Elisabetta
authors: E
authors: Signorino
authors: Ilaria
authors: I
authors: Iacobucci
authors: Annalisa
authors: A
authors: Morano
authors: Luciana
authors: L
authors: De Luca
authors: Pellegrino
authors: P
authors: Musto
authors: Francesco
authors: F
authors: Frassoni
authors: Giuseppe
authors: G
authors: Saglio
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000235:genetics; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D051057:Proto-Oncogene Proteins c-akt