Wnt3A activates canonical Wnt signalling in acute lymphoblastic leukaemia (ALL) cells and inhibits the proliferation of B‐ALL cell lines

• Published in: British journal of haematology 2007-02, Vol.136 (3), p.400-413
• Main Authors: Nygren, Marit Kveine, Døsen, Guri, Hystad, Marit E., Stubberud, Heidi, Funderud, Steinar, Rian, Edith
• Format: Article
• Language: English
• Subjects: acute lymphoblastic leukaemia; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Blotting, Western - methods; Burkitt Lymphoma - genetics; Burkitt Lymphoma - metabolism; Burkitt Lymphoma - pathology; canonical Wnt signallng; Cell Line, Tumor; Cell Proliferation; Gene Expression Profiling; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; microarray analysis; Microscopy, Confocal; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Signal Transduction - physiology; Statistics, Nonparametric; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Cells, Cultured; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Proteins - pharmacology; Wnt-5a Protein; Wnt3 Protein; Wnt3A; Wnt3A Protein; β‐catenin
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2006.06442.x

Summary Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Recently, there has been a growing interest in Wnt signalling in several aspects of cellular development, including cancer formation. Little is known about Wnt signalling in B‐ALL. We investigated whether activation of canonical Wnt signalling could occur in B‐ALL cells and thereby play a potential role in cellular growth and/or survival. This study found that Wnt3A induced β‐catenin accumulation in both primary B‐ALL cells and B‐ALL leukaemia cell lines. Further, Wnt3A was shown to induce nuclear translocation of β‐catenin and TCF/Lef‐1 dependent transcriptions in the B‐ALL cell line Nalm‐6. Examination of the mRNA expression pattern of WNT ligands, FZD receptors and WNT antagonists in Nalm‐6 cells identified a set of ligands and receptors available for signalling, as well as antagonists potentially available for modulating the response. Functional analyses showed that Wnt3A inhibited the proliferation of several, but not all, B‐ALL cell lines studied. Finally, microarray analysis was used to identify several Wnt3A target genes involved in a diverse range of cellular activities, which are potential mediators of the Wnt3A‐restrained proliferation.