Lymphomas ) Gene Rearrangements in Ki - 1 - positive NPM

The (2;5)(p23;q35) translocation which results in the fusion ofthe NPM (nucleophosmin) gene on chromosome 5q35 with the novelALK (anaplas tic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et aI, Science (Washington DC), 263: 1281-1284, 1994] is associated with lU-i (CD3O)-posltlve anaplastic large cell lymphomas (ALCL); a group of morphologicaHy and Immunophenotypically heterogenous high grade las-ge 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 CD3O antigen. Using a DNA probe immediately 5' to the NPM coding sequences, we have examined NPM gene rearrangements by Southern blotting in 5 lU-i-positive lymphoma cell lines carrying a translocation involving the 5q35 breakpoint and in 25 lU-positive lymphoma tumors, including 9 lift Using this method, we detected rearrangements in all cell lines with apparent dustering of the breakpoints. Analysisof 25 lU-i-positive lym phomas 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 ofNPMgene 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.