Literature DB >> 14623330

Involvement of p53 in alpha4beta1 integrin-mediated resistance of B-CLL cells to fludarabine.

María Teresa de la Fuente1, Benito Casanova, Esperanza Cantero, Mercedes Hernández del Cerro, José Garcia-Marco, Augusto Silva, Angeles Garcia-Pardo.   

Abstract

We recently showed that alpha4beta1 integrin induces B-cell chronic lymphocytic leukemia (B-CLL) cell resistance to fludarabine-induced apoptosis via upregulation of Bcl-xL. We have now studied whether p53 was involved in this response. Cells from five B-CLL patients with wild-type p53 determined by DNA sequencing, or from the EHEB cell line, cultured on the alpha4beta1 ligand H/89 during fludarabine treatment, showed significantly higher viability (P<or=0.001) than cells cultured on poly-D-lysine (pLys). Parallel to this different viability, fludarabine increased p53 expression on pLys-cultured cells and this increase was significantly reduced (P<or=0.05) on cells cultured on H/89. Thus, p53 appears to be part of the survival pathway induced by alpha4beta1 ligation and may contribute to the progressive drug resistance in B-CLL.

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Year:  2003        PMID: 14623330     DOI: 10.1016/j.bbrc.2003.10.054

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  14 in total

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