Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia. (November 2013)

• Record Type: Journal Article
• Authors: Ardjmand, Alireza; de Bock, Charles E.; Shahrokhi, Somayeh; Lincz, Lisa F.; Boyd, Andrew W.; Burns, Gordon F.; Thorne, Rick F.
• Is Part Of: Hematology. Volume 18:Number 6(2013)
• Page Start: 315
• Page End: 322
• Publication Date: 2013-11
• Subjects: Acute lymphoblastic leukemia -- Fat cadherins -- Minimal residual disease -- Pre-B-ALL -- T-ALL; Blood -- Diseases -- Periodicals; Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; 616.15005
• DOI: 10.1179/1607845413Y.0000000080
• Languages: English
• ISSNs: 1024-5332

Abstract

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.