NUCLEOLAR LOCALIZATION OF THE NUCLEOPHOSMIN ANAPLASTIC LYMPHOMA KINASE IS NOT REQUIRED FOR MALIGNANT TRANSFORMATION

The (2;5)(p23;q35) lymphoma-associated chromosomal translocation creat es a novel fusion gene that incorporates parts of the anaplastic lymph oma kinase (ALK) receptor tyrosine kinase and nucleophosmin genes, We report here that the product of this fusion gene accumulates within th e nucleoli of neoplastic cells, and that previous reports of a predomi nantly cytoplasmic localization for the protein represent a tissue-pro cessing artifact, However, nucleolar accumulation of nucleophosmin-ALK may not be necessary for its oncogenic action, because an ALK protein expressed in a lymphoma carrying a variant (1;2) chromosomal transloc ation did not accumulate in nucleoli, Furthermore, an engineered hybri d TPR-ALK protein can transform rodent fibroblasts and produce lymphom as in mice while remaining confined to the cytoplasm, We propose that the transforming action of ALK may not be reliant on its nucleolar loc alization, a hypothesis that may have implications for studies of othe r proteins involved in oncogenesis that are relocalized after the crea tion of fusion genes.