Activation of Wnt/beta-catenin pathway mediates growth and survival in B-cell progenitor acute lymphoblastic leukaemia.

Abstract:

:This study investigated the response of acute lymphoblastic leukaemia (ALL) cells to Wnt proteins. Accumulation of beta-catenin was measured by Western blotting and immunofluorescence microscopy. Reverse transcription polymerase chain reaction (RT-PCR) analysis of B-cell progenitor acute lymphoblastic leukaemia (ALL) cells revealed expression of Wnt genes, including WNT2B in 33%, WNT5A in 42%, WNT10B in 58% and WNT16B in 25% of cases. The Wnt receptors, (Frizzled) FZD7 and FZD8 were also expressed in most cases while FZD3, FZD4 and FZD9 were occasionally detected. Stimulation of ALL cells with Wnt-3a activated canonical Wnt signalling with increased expression and nuclear translocation of beta-catenin. This resulted in a 1.7- to 5.3-fold increase in cell proliferation, which was associated with enhanced cell cycle entry. A significant increase in the survival of ALL cells under conditions of serum deprivation was also observed. Microarray analysis and quantitative RT-PCR revealed that activation of the Wnt/beta-catenin pathway led to altered expression of genes involved in cell cycle regulation and apoptosis in normal and leukaemic B-cell progenitors. Our results demonstrate that Wnt-3a provides proliferative and survival cues in ALL cells. This data suggests that targeting the Wnt signalling pathway may be a useful therapeutic strategy in ALL.

journal_name

Br J Haematol

authors

Khan NI,Bradstock KF,Bendall LJ

doi

10.1111/j.1365-2141.2007.06667.x

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

338-48

issue

3

eissn

0007-1048

issn

1365-2141

pii

BJH6667

journal_volume

138

pub_type

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