Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia

Leuk Res. 2013 May;37(5):520-30. doi: 10.1016/j.leukres.2013.01.014. Epub 2013 Feb 12.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Enzyme Activation / genetics
  • Female
  • GRB2 Adaptor Protein / genetics
  • GRB2 Adaptor Protein / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Leukemic*
  • HEK293 Cells
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • MAP Kinase Signaling System*
  • Male
  • Mice
  • NIH 3T3 Cells
  • Protein-Tyrosine Kinases / biosynthesis*
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism


  • Antigens, CD34
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Proto-Oncogene Proteins c-akt