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Inhibition of Wnt16 in human acute lymphoblastoid leukemia cells containing the t(1;19) translocation induces apoptosis.
- Source :
-
Oncogene [Oncogene] 2005 Aug 11; Vol. 24 (34), pp. 5396-400. - Publication Year :
- 2005
-
Abstract
- The Wnt family of secreted glycoproteins is widely involved in cell proliferation, differentiation and oncogenesis. Many Wnt signaling genes are upregulated and activated in chronic lymphocytic leukemia. Less is known concerning acute leukemia. One subtype of acute lymphoblastoid leukemia (ALL) is characterized by a t(1;19) chromosomal translocation resulting in a fusion protein E2A-Pbx1 that promotes transformation and leukemogenesis. Wnt16 has been shown to be targeted by E2A-Pbx1. We performed a differential gene expression array in acute leukemia cell lines displaying or not displaying the t(1;19) translocation. We found that Wnt16 and many Wnt signaling-related genes were upregulated in the translocation-containing cells. As two isoforms of Wnt16, Wnt16a and Wnt16b, have been recently identified, we demonstrated by using RT-PCR and Western blot that Wnt16b (and not Wnt16a) is overexpressed in t(1;19)-containing cell lines. We then directly addressed the role played by both isoforms in this type of leukemia. Using specific short interfering RNA (siRNA) and an anti-Wnt16 antibody, we showed that targeted-Wnt16b inhibition leads to apoptotic cell death. We also demonstrated that Wnt16b mediates its effect through the canonical Wnt pathway involving dishevelled-2, beta-catenin and survivin. We thus propose that Wnt16 plays an important role in leukemogenesis, raising its therapeutic interest.
- Subjects :
- Gene Expression Profiling
Glycoproteins biosynthesis
Glycoproteins genetics
Humans
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Up-Regulation
Wnt Proteins
Apoptosis genetics
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 19
Glycoproteins physiology
Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology
Translocation, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 24
- Issue :
- 34
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 16007226
- Full Text :
- https://doi.org/10.1038/sj.onc.1208568