NPM ALK GENE FUSION TRANSCRIPTS IDENTIFY A DISTINCT SUBGROUP OF NULL TYPE KI-1 POSITIVE ANAPLASTIC LARGE-CELL LYMPHOMAS/

The chromosomal aberration t(2;5) resulting in the juxtaposition of NP M and ALK genes is a well-known feature of several Ki-1(+) anaplastic large cell lymphomas (ALCL) of the T-cell type. However, conflicting r esults have been reported concerning the presence of this gene rearran gement in other ALCL and Hodgkin's disease (HD), respectively. We perf ormed NPM/ALK RT-PCR on 14 cases of ALCL expressing distinct myelomono cytic markers, e.g, CD11c, CD13, CD14 or CD68, but neither T-cell nor B-cell associated antigens (null cell phenotype). The specific translo cation was found exclusively in six childhood tumours previously diagn osed as malignant histiocytosis (MH), whereas all adult lymphomas (thr ee ALCL without characteristics of MH, three secondary ALCL following HD) and two paediatric cases of secondary ALCL following HD did not sh ow NPM/ALK gene fusion products. By Southern blotting, the status of T -cell receptor (TCR) and immunoglobulin heavy chain genes (IgH) were i nvestigated; two patients with initially diagnosed MW had the TCR delt a-chain gene rearranged (D delta 2-D delta 3 and V delta 1-J delta 1, respectively). IgH rearrangements were detected in only one patient wi th secondary ALCL. Our data indicate a high association of previously diagnosed MH and NPM/ALK gene rearrangements. In one case, this specif ic translocation was demonstrated at an early stage of development; in another, a mature TCR delta-chain gene rearrangement was detected. Th ese data support the hypothesis of a lymphoid origin of this subgroup of Ki-l positive ALCL previously diagnosed as MH.