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Published January 1, 2014 | Version v1
Journal article Open

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

Creators

  • 1. Istanbul Univ, Inst Expt Med, Dept Genet, TR-34093 Istanbul, Turkey
  • 2. Istanbul Univ, Cerrahpasa Med Fac, Dept Pediat Hematol, TR-34093 Istanbul, Turkey
  • 3. Istanbul Univ, Istanbul Fac Med, Dept Pediat Hematol, TR-34093 Istanbul, Turkey
  • 4. Istanbul Kanuni Sultan Suleyman Educ & Res Hosp, Pediat Hematol Div, Istanbul, Turkey
  • 5. Istanbul Okmeydani Educ & Res Hosp, Pediat Hematol Div, Istanbul, Turkey
  • 6. Sisli Etfal Educ & Res Hosp, Minist Hlth, Pediat Hematol Div, Istanbul, Turkey
  • 7. Medeniyet Univ, Fac Med, Pediat Hematol Div, Istanbul, Turkey
  • 8. Kocaeli Univ, Fac Med, Pediat Hematol Div, Kocaeli, Turkey
  • 9. Erasmus MC, Dept Immunol, Rotterdam, Netherlands

Description

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.

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