Submitted November 27, 2007
Accepted April 26, 2009
IGF-IR tyrosine kinase interacts with NPM-ALK oncogene to induce survival of T-cell ALK+ anaplastic large-cell lymphoma cells
Ping Shi, Raymond Lai, Quan Lin, Abid S. Iqbal, Leah C. Young, Larry W. Kwak, Richard J. Ford, and Hesham M. Amin*
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States
Department of Laboratory Medicine and Pathology, The University of Alberta, Edmonton, Alberta, Canada
Department of Medical Genetics, The University of Alberta, Edmonton, Alberta, Canada
Department of Lymphoma and Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States
* Corresponding author; email: hamin{at}mdanderson.org.
Type I insulin-like growth factor receptor (IGF-IR) tyrosine kinase plays important roles in the pathogenesis of several malignancies. Although it promotes the growth of stimulated hematopoietic cells, a direct role of IGF-IR in malignant lymphoma has not been identified. Anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALK+ ALCL) is a unique type of T-cell lymphoma. Approximately 85% of ALK+ ALCL cases harbor the translocation t(2;5)(p23;q35), which generates the chimeric oncogene NPM-ALK. In the present study, we explored a possible role of IGF-IR in ALK+ ALCL. Our results demonstrate that IGF-IR and IGF-I are widely expressed in ALK+ ALCL cell lines and primary tumors. Importantly, we identified novel reciprocal functional interactions between IGF-IR and NPM-ALK. Antagonism of IGF-IR decreased the viability, induced apoptosis and cell-cycle arrest, and decreased proliferation and colony formation of ALK+ ALCL cell lines. These effects could be explained by alterations of cell survival regulatory proteins downstream of IGF-IR signaling. Our findings improve current understanding of the biology of IGF-IR and NPM-ALK and have significant therapeutic implications as they identify IGF-IR signaling as a potential therapeutic target in ALK+ ALCL and possibly other types of malignant lymphoma.
