Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia

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.