MOLECULAR CHARACTERIZATION OF THE T(2-5)(P23-Q35) TRANSLOCATION IN ANAPLASTIC LARGE-CELL LYMPHOMA (KI-1) AND HODGKINS-DISEASE

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (AL CL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains larg ely uncertain. Classical cytogenetic analysis has shown a unique trans location involving bands 2p23 and 5q35 bands in a variable number of A LCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fus ed genes of t(2;5). To investigate the presence and the precise freque ncy of NPM-ALK gene products among ALCL and HD cases, a large and well -characterized panel of ALCL (n = 49) and HD (n = 72) cases was studie d using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemi stry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosi s and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK tra nscripts by RT-PCR. NPM-ALK gene rearrangements were detected in all R T-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, i n all the available cases we were able to show the presence of ALK-rel ated protein using a specific polyclonal antiserum recognizing the cyt oplasmic domain of ALK by immunohistochemistry. Our data show that NPM -ALK gene transcripts are identified in a subpopulation of ALCL, almos t exclusively in T or null cell in origin, and in rare cases of HD. Th ese findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD. (C) 1996 by The American Society of Hematology.