Invited Speaker

NPM-ALK+ T-Cell lymphoma as a model for developing cancer therapeutics
Hesham M. Amin
USA

NPM-ALK+ (nucleophosmin-anaplastic lymphoma kinase-expressing) T-cell lymphoma is an aggressive malignant disease. Although it affects patients of all ages, NPM-ALK+ T-cell lymphoma tends to occur in children and young adults accounting for 3 - 5% of adults’ and 20 - 30% of children’s non-Hodgkin’s lymphomas, respectively. Current therapeutic approaches are not specific and similar to several other types of malignant lymphoma are based on CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) combination chemotherapy. Initially patients respond favorably to CHOP, but eventually 30 - 40% have a relapse and death is not uncommon. ALK is a receptor tyrosine kinase with structural similarities to the insulin receptor. The physiological expression of ALK is limited to embryonic cells of neural origin. Hence, the expression of ALK in T-cell lymphoma is an aberrant event resulting from the chromosomal translocation t(2;5)(p23;q35), which involves the ALK gene on chromosome 2p23 and the NPM gene on 5q35. This translocation generates the chimeric tyrosine kinase NPM-ALK that carries significant oncogenic effects through collaboration with a comprehensive network of signaling cascades resulting in cell survival and proliferation. NPM-ALK+ T-cell lymphoma is a relatively uncommon type of cancer, but because of the numerous molecular events it could represent an excellent model for the development of novel cancer therapeutics.