title: The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia.
abstract: Improved survival of patients with acute lymphoblastic leukemia (ALL) has emerged from identifying new prognostic markers; however, 20% of children still suffer recurrence. Previously, the altered expression of Fat1 cadherin has been implicated in a number of solid tumors. In this report, in vitro analysis shows that Fat1 protein is expressed by a range of leukemia cell lines, but not by normal peripheral blood (PB) and bone marrow (BM) cells from healthy donors. In silico analysis of expression of array data from clinical leukemias found significant levels of Fat1 transcript in 11% of acute myeloid leukemia, 29% and 63% of ALL of B and T lineages, respectively, and little or no transcript present in normal PB or BM. Furthermore, in two independent studies of matched diagnosis-relapse of precursor B-cell (preB) ALL pediatric samples (n=32 and n=27), the level of Fat1 mRNA expression was prognostic at the time of diagnosis. High Fat1 mRNA expression was predictive of shorter relapse-free and overall survival, independent of other traditional prognostic markers, including white blood cell count, sex and age. The data presented demonstrate that Fat1 expression in preB-ALL has a role in the emergence of relapse and could provide a suitable therapeutic target in high-risk preB-ALL.
authors: Cancer Research Unit, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors: C E
authors: CE
authors: de Bock
authors: A
authors: A
authors: Ardjmand
authors: T J
authors: TJ
authors: Molloy
authors: S M
authors: SM
authors: Bone
authors: D
authors: D
authors: Johnstone
authors: D M
authors: DM
authors: Campbell
authors: K L
authors: KL
authors: Shipman
authors: T M
authors: TM
authors: Yeadon
authors: J
authors: J
authors: Holst
authors: M D
authors: MD
authors: Spanevello
authors: G
authors: G
authors: Nelmes
authors: D R
authors: DR
authors: Catchpoole
authors: L F
authors: LF
authors: Lincz
authors: A W
authors: AW
authors: Boyd
authors: G F
authors: GF
authors: Burns
authors: R F
authors: RF
authors: Thorne
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002648:Child; D016147:Genes, Tumor Suppressor; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D015820:Cadherins; C502403:FAT1 protein, human; D012333:RNA, Messenger