UNIFORM EXPRESSION OF CYTOTOXIC MOLECULES IN ANAPLASTIC LARGE-CELL LYMPHOMA OF NULL T-CELL PHENOTYPE AND IN CELL-LINES DERIVED FROM ANAPLASTIC LARGE-CELL LYMPHOMA

We recently provided ample evidence that anaplastic large cell lymphom as of T/null phenotype (T-/null-ALCL) genotypically represent peripher al T cell lymphomas which in up to 90% have a phenotype of cytotoxic c ells with expression of granzyme B protein and perforin transcripts. H owever, the issue of granzyme B expression in T-/null-ALCL is still co ntroversial due to differing results from another laboratory. To verif y our earlier immunohistochemical stainings for granzyme B, we looked for granzyme B transcripts by in situ hybridization (ISH). In addition , we investigated our previously analyzed cases by immunohistology (IH ) with another antibody (2G9), which reacts with two molecules known t o be expressed in cytotoxic cells: T-cell-restricted intracellular ant igen (TIA)-1 and granule membrane protein-17 (GMP-17). We also extende d our studies to homogenous tumor cell populations provided by ALCL-de rived cell lines. As evidenced by ISH, transcripts for perforin, TIA-1 and granzyme B were found in all ALCL-derived cell lines. Similarly, proteins of TIA-1/GMP-17, granzyme B and perforin were expressed in al l of these lines as shown by IH. In biopsy specimens, TIA-1/GMP-17 wer e detected by IH in 14/16 cases of T-/null-ALCL, and granzyme B transc ripts were found in 13/13 T-/null-ALCL cases, but not in 6 B-ALCL case s. The detection of granzyme B transcripts yielded results largely ide ntical to those of IH for granzyme B protein, thus confirming our earl ier data and suggesting that the regulation of the expression of this molecule largely occurs at the transcriptional level. Our data further confirm the almost uniform expression of cytotoxic molecules in both primary ALCL cases and ALCL-derived cell lines and therefore suggest t hat the derivation from cytotoxic T cells may be the unifying characte ristic for T-/null-ALCL.