BMSEHA15
Published online 9 February 2010
(Haematologica 2010, 10.3324/haematol.2009.013995)
Copyright © 2010 by Ferrata Storti Foundation
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Article

CXCL12-induced chemotaxis is impaired in T cells from ZAP-70- chronic lymphocytic leukemia patients

Mercedes Borge1, Paula Romina Nannini1, Jeremías Gastón Galletti1, Pablo Elías Morande1, Julio Sánchez Ávalos2, Raimundo Fernando Bezares3, Mirta Giordano1,4, Romina Gamberale1,4

1 Laboratorio de Inmunología Oncológica, IIHema, Academia Nacional de Medicina
2 Instituto Alexander Fleming, Ciudad de Buenos Aires
3 Hospital General de Agudos Dr. T. Álvarez, Ciudad de Buenos Aires, Argentina
4 Departamento de Microbiología Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires

Correspondence: Romina Gamberale, Laboratorio de Inmunología Oncológica, Academia Nacional de Medicina, Pacheco de Melo 3081 (1425) Ciudad de Buenos Aires, Argentina. Tel: 54 11 4805 3411 FAX: 54 11 4803 9475 E-mail: rominagamberale{at}ciudad.com.ar

ABSTRACT

Background: T-cells from chronic lymphocytic leukemia patients may actually play an important role in contributing to the onset, sustenance, and exacerbation of the disease by providing survival and proliferative signals to the leukemic clone within lymph nodes and bone marrow.

Design and methods: By performing chemotaxis assays towards CXCL12, CCL21 and CCL19, we sought to evaluate the migratory potential of T cells from chronic lymphocytic leukemia patients. We next analyzed the chemokine-induced migration of T cells by discriminating chronic lymphocytic leukemia samples according to the expression of the poor prognostic factors CD38 and ZAP-70 in leukemic cells by flow cytometry.

Results: We found that T cells from unsegregated patients are less responsive to these chemokines than T cells from healthy adults despite similar CXCR4 and CCR7 expression. Once segregation of our patients according to ZAP-70 expression was done, we found that T cells from ZAP-70– samples presented a significant lower migration towards CXCL12 compared to ZAP-70+ samples, which was not due to a defective CXCR4 downregulation, F-actin polymerization or to a lesser expression of ZAP-70, CD3, CD45, CD38 or CXCR7 on these cells. Interestingly, we found that leukemic cells from ZAP-70– samples seem to be responsible for the defective CXCR4 migratory response observed in their T cells.

Conclusions: The impaired migration towards CXCL12 may reduce the access of T cells from ZAP-70– patients to lymphoid organs, creating a less favorable microenvironment for leukemic cell survival and proliferation.

Key words: chronic lymphocytic leukemia, T cell chemotaxis, CXCL12, CXCR4.