Overexpression of the giant FAT1 cadherin gene and its prognostic significance in de novo acute leukaemia patients

FAT1 is a type 1 transmembrane protein belonging to the cadherin superfamily. Many reports showed either overexpression of FAT1 gene or its loss in solid cancers. Limited studies evaluated its importance in leukemogenesis. Real-time quantitative reverse transcriptase polymerase chain reaction (RTQ-PCR) was used to examine the levels of FAT1 mRNA expression in 50 paediatric acute lymphoblastic leukaemia (ALL) and 50 adult cytogenetically normal acute myeloid leukaemia (CN-AML). Each group was compared with 20 age- and gender-matched healthy controls. Peripheral blood (PB) samples were collected at time of diagnosis from all patients and controls. FAT1 mRNA was detected in 66% of the paediatric ALL cases, 50% of the adult CN-AML cases, while not expressed in the PB of the control groups. T cell ALL (T-ALL) cases showed high statistical significant difference in the expression levels of FAT1 when compared to B cell precursor (BCP)-ALL (P = 0.001). Paediatric FAT1^high ALL expressors showed poor response to induction therapy than FAT1^low ALL (P = 0.001) as well as FAT1^pos expressors in adult CN-AML when compared to FAT1^neg (P = 0.01). FAT1 plays an important role in leukemogenesis; its expression levels may be used as an independent prognostic indicator in paediatric ALL and may help in distinguishing an important risk group in adult CN-AML.