NUCLEOPHOSMIN (NPM) GENE REARRANGEMENTS IN KI-1-POSITIVE LYMPHOMAS

The (2;5)(p23;q35) translocation which results in the fusion of the NP M (nucleophosmin) gene on chromosome 5q35 with the novel ALK (anaplast ic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et al., Scien ce (Washington DC), 263: 1281-1284, 1994] is associated with Ki-1 (CD3 0)-positive anaplastic large cell lymphomas (ALCL); a group of morphol ogically and immunophenotypically heterogenous high grade large cell l ymphomas (LCL), which share many characteristics with Hodgkin's diseas e (HD), including the presence of variable numbers of Reed-Sternberg-l ike cells and the expression of CD30 antigen. Using a DNA probe immedi ately 5' to the NPM coding sequences, we have examined NPM gene rearra ngements by Southern blotting in 5 Ki-1-positive lymphoma cell lines c arrying a translocation involving the 5q35 breakpoint and in 25 Ki-pos itive lymphoma tumors, including 9 HD. Using this method, we detected rearrangements in all cell lines with apparent clustering of the break points. Analysis of 25 Ki-1-positive lymphomas indicated that only 4 n eoplasms, including two HD, had NPM gene rearrangements. Thus, our fin dings 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.