IN-VIVO PHENOTYPIC CHARACTERIZATIONS OF AKR T-CELL LYMPHOMAS WITH DIFFERENT LEUKEMIC POTENTIAL - POSSIBLE ROLE OF ALPHA-4-BETA-7 INTEGRIN IN THE PROGRESSION TOWARDS THE LEUKEMIC PHENOTYPE

The present study was undertaken in order to determine whether the exp ression of specific surface molecules which mediate immune recognition as well as cell-cell and cell-matrix interactions is associated with the leukemic evolution of T-cell lymphomas. To this end, we have inves tigated the in vivo phenotypic characteristics and the in vitro natura l-killer(NK)-cell susceptibility of a group of MCF-247-induced AKR/J T -cell lymphomas with different leukemic potential. We found that in th e AKR/J model, the biological aggressiveness of leukemic cells is not dependent upon an escape from host immune surveillance as a consequenc e of an in vivo down-regulation of H2-K-k determinants or a resistance to NK lysis. Moreover, NK susceptibility of AKR/J lymphomas does not seem to correlate with the level of H2-antigen expression. No obvious correlation was found between the leukemic phenotype and the amount of MEL-14, LFA-1, ICAM-1, Pgp-1/CD44 and THAM/CD26 antigen expression. A n in vivo coordinated up-regulation of alpha 4 and beta 7 integrin cha ins, with the highest levels of expression detected in secondary sites of leukemic infiltration, was observed in the highly leukemic lymphom a NQ22 and, albeit to a lesser extent, in lymphomas with moderate leuk emic potential. Conversely, non-leukemic lymphomas were repeatedly alp ha 4- and beta 7-negative. These findings suggest that in the AKR/J sy stem the expression of alpha 4 beta 7 integrin may contribute to leuke mic spreading of T-cell lymphomas. (C) 1994 Wiley-Liss, Inc.