Nucleophosmin (NPM) Gene Rearrangements in Ki-l-positive Lymphomas

The (2;5)(p23;q35) translocation which results in the fusion of the NPM (nucleophosmin) gene on chromosome 5q35 with the novel ALK (anaplastic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et al, Science (Washington DC), 263: 1281-1284,1994] is associated with Ki-1 (CD30)-positive anaplastic large cell lymphomas (ALCL); a group of morphologically and immunophenotypically heterogenous high grade large cell lymphomas (LCL), which share many characteristics with Hodgkin's disease (HD), including the presence of variable numbers of Reed-Sternberg-like cells and the expression of CD30 antigen. Using a DNA probe immediately 5' to the NPM coding sequences, we have examined NPM gene rearrangements by Southern blotting in 5 Ki-l-positive lymphoma cell lines carrying a translocation involving the 5q35 breakpoint and in 25 Ki-positive lymphoma tumors, including 9 HD. Using this method, we detected rearrangements in all cell lines with apparent clustering of the breakpoints. Analysis of 25 Ki-l-positive lymphomas indicated that only 4 neoplasms, including two HD, had NPM gene rearrangements. Thus, our findings suggest that only a subset of ALCL has detectable involvement of the NPM gene. In addition, the presence of NPM gene rearrangements in HD indicates the involvement of this gene in a fraction of HD. Thus, NPM gene rearrangements may identify a certain subtype in ALCL and HD which may be closely related.