ALPHA-4-BETA-7 INTEGRIN EXPRESSION IS ASSOCIATED WITH THE LEUKEMIC EVOLUTION OF HUMAN AND MURINE T-CELL LYMPHOBLASTIC LYMPHOMAS

We have previously shown that the in vivo coordinated expression of in dividual alpha 4 and beta 7 integrin chains correlated with the leukem ic potential displayed by cell lines derived from murine lymphoblastic T-cell lymphomas (T-LBLs) when transplanted subcutaneously into synge neic AKR mice. In the present study, by using immunofluorescence and i mmunocytochemical analyses, we have confirmed that the in vivo up-regu lation of the alpha 4 beta 7 heterodimeric complex is associated with the leukemic behavior of AKR T-LBLs. In addition, when compared with t he parental, highly leukemic NQ22 cells, the variant cell line NQ22V e xhibited a reduced leukemic potential that was invariably associated w ith a delayed alpha 4 beta 7 up-regulation in vivo. Moreover, the leuk emic cell line SJ-1, derived from a spontaneous T-LBL of the SJL strai n, also displayed high levels of alpha 4 beta 7 expression with a patt ern of tissue distribution similar to that of NQ22 cells from leukemic AKR animals. Of note, in most of the tissues involved by murine T-LBL dissemination, and particularly in liver, kidney, and lung, alpha 4 b eta 7-positive leukemic cells were always located around strongly VCAM -1-positive vascular spaces. These findings are consistent with a poss ible role of alpha 4 beta 7/VCAM-1 interactions in the extravasation a nd, consequently, in the leukemic dissemination of murine T-LBL cells. Immunocytochemical analysis carried out in 11 human T-LBLs showed tha t pathological lymph nodes from all 7 cases with bone marrow infiltrat ion at presentation carried alpha 4 beta 7-posiitve cells, whereas all 4 aleukemic T-LBLs were repeatedly alpha 4 beta 7 negative, also in m etachronous lesions. These findings suggest that alpha 4 beta 7-positi ve human T-LBLs may represent a distinct clinicopathological entity. I n addition, alpha 4 beta 7 expression was significantly more prevalent in younger patients (<11 years; P = 0.02), further supporting such a hypothesis. Moreover, as in murine T-LBLs , the pattern of alpha 4 bet a 7 positivity in involved lymph nodes was mainly focal, whereas nearl y all neoplastic cells infiltrating bone marrow expressed this integri n, suggesting a possible role for alpha 4 beta 7 in the leukemic disse mination also of human T-LBLs.