Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

OH Ng, Y Erbilgin, S Firtina, T Celkan, Z Karakas, G (G.) Aydogan, E Turkkan, Y Yildirmak, C Timur, E Zengin, Jacques Dongen, Frank Staal, U (Ugur) Ozbek, M Sayitoglu

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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.
Original languageUndefined/Unknown
Number of pages8
JournalBlood Cancer Journal
Volume4
DOIs
Publication statusPublished - 2014

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