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 individual alpha 4 and beta 7 integrin chains correlated with the leukemic potential displayed by cell lines derived from murine lymphoblastic T-cell lymphomas (T-LBLs) when transplanted subcutaneously into syngeneic AKR mice. In the present study, by using immunofluorescence and immunocytochemical analyses, we have confirmed that the in vivo up-regulation of the alpha 4 beta 7 heterodimeric complex is associated with the leukemic behavior of AKR T-LBLs. In addition, when compared with the parental, highly leukemic NQ22 cells, the variant cell line NQ22V exhibited a reduced leukemic potential that was invariably associated with a delayed alpha 4 beta 7 up-regulation in vivo Moreover, the leukemic cell line SJ-1, derived from a spontaneous T-LBL of the SJL strain, also displayed high levels of alpha 4 beta 7 expression with a pattern 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 beta 7-positive leukemic cells were always located around strongly VCAM-1-positive vascular spaces. These findings are consistent with a possible role of alpha 4 beta 7/VCAM-1 interactions in the extravasation and, consequently, in the leukemic dissemination of murine T-LBL cells. Immunocytochemical analysis carried out in 11 human T-LBLs showed that pathological lymph nodes from all 7 cases with bone marrow infiltration at presentation carried alpha 4 beta 7-positive cells, whereas all 4 aleukemic T-LBLs were repeatedly alpha 4 beta 7 negative, also in metachronous lesions. These findings suggest that alpha 4 beta 7-positive human T-LBLs may represent a distinct clinicopathological entity. In 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 beta 7 positivity in involved lymph nodes was mainly focal, whereas nearly all neoplastic cells infiltrating bone marrow expressed this integrin, suggesting a possible role for alpha 4 beta 7 in the leukemic dissemination also of human T-LBLs.
Dolcetti
R
R
Division of Experimental Oncology 1, IRCCS, Aviano (PN), Italy.
Giardini
R
R
Doglioni
C
C
Cariati
R
R
Pomponi
F
F
D'Orazi
C
C
Rao
S
S
Lazarovits
A I
AI
Butcher
E C
EC
Boiocchi
M
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016023:Integrins / Q000096:biosynthesis*; D015458:Leukemia, T-Cell / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D016023:Integrins; C071777:integrin alpha4beta7