Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia


Ng Ö. , Erbilgin Y., Firtina S., Celkan T., Karakas Z., Aydogan G., ...More

Blood Cancer Journal, vol.4, no.3, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 4 Issue: 3
  • Publication Date: 2014
  • Doi Number: 10.1038/bcj.2014.12
  • Title of Journal : Blood Cancer Journal
  • Keywords: BETA-CATENIN MUTATION, TRANSCRIPTION FACTOR, EXPRESSION, GENE, ACTIVATION, TRANSFORMATION, THYMOCYTES, CARCINOMA, PATHWAYS

Abstract

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated beta-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in similar to 40% of the patients. When beta-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.