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Title: The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance
Authors: Thiago, Leandro de Souza
Costa, Elaine Sobral da
Lopes, Daiana Vieira
Otazú, Ivone Beatriz
Nowill, Alexandre Eduardo
Mendes, F. A.
Portilho, Márcio Figueiredo
Abreu Junior, Jose Garcia Ribeiro
Mermelstein, Claudia dos Santos
Orfao, A.
Rossi, Maria Isabel Doria
Borojevic, Radovan
Keywords: Leucemia linfoblástica aguda
Via de sinalização WNT
Issue Date: 2010
Citation: THIAGO, L. S. et al. The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance. Biomedicine & Pharmacotherapy, v. 64, p. 63-72, 2010.
Abstract: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children. The Wnt signaling pathway has been found to be extensively involved in cancer onset and progression but its role in BCP-ALL remains controversial.Weevaluate the role of the Wnt pathway in maintenance of BCP-ALL cells and resistance to chemotherapy. Gene expression profile revealed that BCP-ALL cells are potentially sensitive to modulation of Wnt pathway. Nalm-16 and Nalm-6 cell lines displayed low levels of canonical activation, as reflected by the virtually complete absence of total b-catenin in Nalm-6 and the b-catenin cell membrane distribution in Nalm-16 cell line. Canonical activation with Wnt3a induced nuclear b-catenin translocation and led to BCP-ALL cell death. Lithium chloride (LiCl) also induced a cytotoxic effect on leukemic cells. In contrast, both Wnt5a and Dkk-1 increased Nalm-16 cell survival. Also, Wnt3a enhanced the in vitro sensitivity of Nalm-16 to etoposide (VP-16) while treatment with canonical antagonists protected leukemic cells from chemotherapy-induced cell death. Overall, our results suggest that canonical activation of the Wnt pathway may exerts a tumor suppressive effect, thus its inhibition may support BCP-ALL cell survival.
Description: 10 p. : il.
Document type: Artigo / Article
Unit: Diretoria de Programa - DIPRO
Appears in Collections:DIMAV | Artigos publicados em periódicos internacionais

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