The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance
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Abstract
10 p. : il.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