title: Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia.
abstract: Measurement of minimal residual disease (MRD) maintains an important role in the clinical management of acute lymphoblastic leukemia (ALL). Recently, we identified Fat1 cadherin as a unique and independent prognostic factor for relapse-free and overall survival in pediatric pre-B-ALL. Here, we analyzed Fat1 mRNA for its potential as a novel marker of MRD in cases of pre-B- and T-ALL. Analyses of microarray data from 125 matched diagnosis/relapse samples across three independent datasets indicate that Fat1 mRNA is detectable in an average of 31.3% of diagnosed pre-B-ALL, of which 67.5% of cases remained positive at relapse. Furthermore, some 20% of cases with undetectable levels of Fat1 mRNA at diagnosis became positive upon relapse. T-ALL cases were 83.3% positive for Fat1 expression at diagnosis with 77.7% remaining positive at relapse. Towards proof of concept, we developed a quantitative polymerase chain reaction assay and demonstrate detection of Fat1 mRNA in leukemic cells mixed with normal peripheral blood cells at a sensitivity of 1 in 10 000 to 100 000 cells. Fat1 may therefore provide a new marker of MRD for patients with ALL lacking known genomic aberrations or within a multiplex approach to MRD detection.
authors: University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
authors: Alireza
authors: A
authors: Ardjmand
authors: Charles E
authors: CE
authors: de Bock
authors: Somayeh
authors: S
authors: Shahrokhi
authors: Lisa F
authors: LF
authors: Lincz
authors: Andrew W
authors: AW
authors: Boyd
authors: Gordon F
authors: GF
authors: Burns
authors: Rick F
authors: RF
authors: Thorne
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D015870:Gene Expression; D006801:Humans; D046228:Microarray Analysis; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C502403:FAT1 protein, human; D012333:RNA, Messenger