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ACUTE LEUKEMIA

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

, , , , , & show all
Pages 315-322 | Published online: 15 Nov 2013
 

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.

Acknowledgements

This work was supported by grants from the National Health and Medical Research Council, Australia (455531), Hunter Medical Research Institute (HMRI-09-23) sponsored by Gallerie Fine Jewellery), the Hunter Children's Research Foundation, and the Leukemia Foundation Australia. AA is the recipient of the Arrow Bone Marrow Transplant Foundation Scholarship. RFT was awarded a Career Development Fellowship by the Cancer Institute NSW.

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