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

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support SIMILAR CONTENT BEING VIEWED BY OTHERS TRANSCRIPTOMIC CLASSES OF _BCR-ABL1_ LYMPHOBLASTIC LEUKEMIA Article Open access 19 June 2023 _FAT1_ EXPRESSION IN T-CELL ACUTE LYMPHOBLASTIC

LEUKEMIA (T-ALL) MODULATES PROLIFERATION AND WNT SIGNALING Article Open access 18 January 2023 INTEGRATED STEM CELL SIGNATURE AND CYTOMOLECULAR RISK DETERMINATION IN PEDIATRIC ACUTE MYELOID

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CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We are grateful to Dheepa Bhojwani who made clinical outcome data available. We thank Professor Murray

Norris for his comments and critical review of the manuscript. This work was supported by a project grant from the National Health and Medical Research Council, Australia (455531), Hunter

Medical Research Institute (HMRI-09-23 kindly sponsored by Gallerie Fine Jewellery) and the Leukaemia Foundation Australia. RFT was awarded a career development fellowship by the Cancer

Institute NSW. AA is in receipt of the Arrow Bone Marrow Transplant Foundation Scholarship. AUTHOR INFORMATION Author notes * C E de Bock and A Ardjmand: These authors contributed equally to

this study. AUTHORS AND AFFILIATIONS * Cancer Research Unit, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia C E de Bock, A

Ardjmand, S M Bone, D M Campbell, K L Shipman, G F Burns & R F Thorne * Leukaemia Foundation of Queensland Research Unit, Queensland Institute of Medical Research, Brisbane, Queensland,

Australia C E de Bock, T M Yeadon, M D Spanevello & A W Boyd * Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia C E de Bock, A Ardjmand, S M Bone, D

Johnstone, D M Campbell, K L Shipman, L F Lincz, G F Burns & R F Thorne * Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia T J Molloy *

Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, University of Newcastle, Callaghan, New South Wales, Australia D Johnstone * Gene and Stem Cell Therapy

Program, Centenary Institute, Newtown, New South Wales, Australia J Holst * Tumour Bank, Children's Hospital at Westmead, Westmead, New South Wales, Australia G Nelmes & D R

Catchpoole * Hunter Haematology Research Group, Calvary Mater Newcastle Hospital, Waratah, New South Wales, Australia L F Lincz Authors * C E de Bock View author publications You can also

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PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE de Bock, C., Ardjmand, A., Molloy, T. _et al._ The Fat1 cadherin is overexpressed and an independent prognostic

factor for survival in paired diagnosis–relapse samples of precursor B-cell acute lymphoblastic leukemia. _Leukemia_ 26, 918–926 (2012). https://doi.org/10.1038/leu.2011.319 Download

citation * Received: 01 March 2011 * Revised: 29 August 2011 * Accepted: 21 September 2011 * Published: 25 November 2011 * Issue Date: May 2012 * DOI: https://doi.org/10.1038/leu.2011.319

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