FUSION OF A KINASE GENE, ALK, TO A NUCLEOLAR PROTEIN GENE, NPM, IN NON-HODGKINS-LYMPHOMA

The 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This re arrangement was shown to fuse the NPM nucleolar phosphoprotein:gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23. In the predicted hybrid protein, the am ino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK). Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greates t sequence similarity to the insulin receptor subfamily of kinases. Un scheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.