The role of nucleophosmin fusion sequences in the oncogenic activation of the (2;5) translocation protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, South Africa, in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 1996The NPM-ALK fusion gene, formed by the t(2;5)(p23;q35) in non-Hodgkin's lymphoma encodes a 75kDa hybrid protein that contains the amino-terminal 118 amino acid residues of the nucleolar phosphoprotein nucleophosmin (NPM) joined to the entire cytoptasmic portion of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK). The transforming ability of NPM-ALK is demonstrated and it is shown that oncogenesis by the chimaeric protein requires the activation of its kinase function as a result of oligomerisation mediated by the NPM segment. [Abbreviated Abstract. Open document to view full version