Detection of the t(2;5)-associated NPM/ALK fusion cDNA in peripheral bloodcells of healthy individuals

The translocation t(2;5), which leads to the fusion of the nucleophosmin ge ne (NPM) on chromosome 5q35 to the receptor kinase ALK on chromosome 2p23, is found in CD30(+) anaplastic large cell lymphomas and some cases of B-cel l lymphoma. Hodgkin's disease (HD) is a malignant lymphoma characterized by large multinucleated tumour cells, Hodgkin and Reed-Sternberg (H&RS) cells , surrounded by a dense lymphohistiocytic infiltrate. Our group recently de monstrated NPM/ALK fusion cDNAs by single-cell RT-PCR in < 3% of CD30(+) tu mour cells in 2/9 cases of HD. To further delineate the relevance of this f inding for HD, we studied the occurrence of NPM/ALK fusion genes in periphe ral blood cells of healthy donors by RT-PCR. NPM/ALK fusion cDNAs were foun d by RT-PCR in 14/29 healthy individuals and confirmed by hybridization wit h a breakpoint-specific oligonucleotide. Due to the low rate of NPM/ALK-pos itive cells in the peripheral blood of positive individuals, an assignment to a defined cellular subpopulation was not possible. We conclude that NPM/ ALK fusion genes are present in peripheral blood cells of healthy donors. A fter t(14;18) and t(9;22), t(2;5) represents the third example of tumour-as sociated translocation products in blood cells of apparently healthy donors . The implications of this finding are discussed.