Abstract |
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.
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Authors | R Dolcetti, R Giardini, C Doglioni, R Cariati, F Pomponi, C D'Orazi, S Rao, A I Lazarovits, E C Butcher, M Boiocchi |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 150
Issue 5
Pg. 1595-605
(May 1997)
ISSN: 0002-9440 [Print] United States |
PMID | 9137086
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Integrins
- integrin alpha4beta7
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Topics |
- Adolescent
- Adult
- Animals
- Child
- Child, Preschool
- Evolution, Molecular
- Female
- Humans
- Immunophenotyping
- Integrins
(biosynthesis)
- Leukemia, T-Cell
(etiology, metabolism, pathology)
- Male
- Mice
- Mice, Inbred AKR
- Mice, Inbred C57BL
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(etiology, metabolism, pathology)
- Tumor Cells, Cultured
- Up-Regulation
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