title: Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling.
abstract: B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Shyh-Shin
authors.initials: SS
authors.lastname: Chiou
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Wang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Shih-Bo
authors.initials: SB
authors.lastname: Huang
authors.affiliation: Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Department of Surgery, Faculty of Medicine Kaohsiung 807, Taiwan and Division of Hepatobiliary Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Shen-Nien
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liao
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Kwei-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, jackhsu@kmu.edu.tw.
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D023041:Xenograft Model Antitumor Assays
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C549111:WLS protein, human