4ß1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine
* Departamento de Inmunología, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain; and
Servicio de Hematología, Hospital Universitario Clínica Puerta de Hierro, Madrid, Spain
Correspondence: Dr. Angeles Garcia-Pardo, Centro de Investigaciones Biológicas, CSIC, Velázquez 144, 28006 Madrid, Spain. E-mail: agarciapardo{at}cib.csic.es
B-cell chronic lymphocytic leukemia is characterized by the
accumulation of malignant B lymphocytes as a result of abnormal
survival signals operating in vivo. Previously, we showed that adhesion
of B-CLL cells to the fibronectin fragment H89, a ligand for 
4ß1
integrin, prevents their spontaneous apoptosis in vitro. We have now
studied whether 4ß1/H89 interaction affected the response of B-CLL
cells to the therapeutic drug fludarabine. B-CLL cells cultured on H89
during treatment with fludarabine showed significantly higher mean
viability (P<0.05) than cells cultured on the control
polylysine for all doses of drug tested. Similar results were obtained
with the EHEB cell line. Analysis of the expression of Bcl-2-family
proteins after 48 h of fludarabine treatment revealed that Bcl-xL
levels were significantly higher (P<0.05) for cells
cultured on H89 than on polylysine and correlated (r=0.56,
P<0.05) with the increased cell viability observed on H89
cultures. These results indicate that Bcl-xL is involved in the
survival signals induced by 4ß1 ligation and may contribute
to the progressive drug resistance observed in B-CLL.
Key Words: integrin signaling • apoptosis • drug resistance • Bcl-xL
This article has been cited by other articles:
 |
|
 |
|
  B. Stamatopoulos, B. Haibe-Kains, C. Equeter, N. Meuleman, A. Soree, C. De Bruyn, D. Hanosset, D. Bron, P. Martiat, and L. Lagneaux Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA Haematologica, June 1, 2009; 94(6): 790 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zucchetto, D. Benedetti, C. Tripodo, R. Bomben, M. Dal Bo, D. Marconi, F. Bossi, D. Lorenzon, M. Degan, F. M. Rossi, et al. CD38/CD31, the CCL3 and CCL4 Chemokines, and CD49d/Vascular Cell Adhesion Molecule-1 Are Interchained by Sequential Events Sustaining Chronic Lymphocytic Leukemia Cell Survival Cancer Res., May 1, 2009; 69(9): 4001 - 4009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Redondo-Munoz, E. Escobar-Diaz, R. Samaniego, M. J. Terol, J. A. Garcia-Marco, and A. Garcia-Pardo MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by {alpha}4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration Blood, November 1, 2006; 108(9): 3143 - 3151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Olson, L. C. Burkly, D. R. Leone, B. M. Dolinski, and R. R. Lobb Anti-{alpha}4 integrin monoclonal antibody inhibits multiple myeloma growth in a murine model Mol. Cancer Ther., January 1, 2005; 4(1): 91 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Durig, H. Nuckel, A. Huttmann, E. Kruse, T. Holter, K. Halfmeyer, A. Fuhrer, R. Rudolph, N. Kalhori, A. Nusch, et al. Expression of ribosomal and translation-associated genes is correlated with a favorable clinical course in chronic lymphocytic leukemia Blood, April 1, 2003; 101(7): 2748 - 2755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Keating, N. Chiorazzi, B. Messmer, R. N. Damle, S. L. Allen, K. R. Rai, M. Ferrarini, and T. J. Kipps Biology and Treatment of Chronic Lymphocytic Leukemia Hematology, January 1, 2003; 2003(1): 153 - 175. [Abstract] [Full Text] [PDF]
|
|
