title: Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.
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 β-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 ∼40% of the patients. When β-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.
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: O H
authors.initials: OH
authors.lastname: Ng
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Erbilgin
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Firtina
authors.affiliation: Department of Pediatrics Hematology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Celkan
authors.affiliation: Department of Pediatric Hematology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Z
authors.initials: Z
authors.lastname: Karakas
authors.affiliation: Pediatric Hematology Division, Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Aydogan
authors.affiliation: Pediatric Hematology Division, Istanbul Okmeydani Education and Research Hospital, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Turkkan
authors.affiliation: Pediatric Hematology Division, Ministry of Health Sisli Etfal Education and Research Hospital, Istanbul, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Yildirmak
authors.affiliation: Pediatric Hematology Division, Medeniyet University Medical Faculty, Istanbul, Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Timur
authors.affiliation: Pediatric Hematology Division, Kocaeli University Medical Faculty, Kocaeli, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Zengin
authors.affiliation: Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: 1] Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: F J T
authors.initials: FJ
authors.lastname: Staal
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: U
authors.initials: U
authors.lastname: Ozbek
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Sayitoglu