PROGNOSTIC IMPACT OF FAT1 CADHERIN EXPRESSION IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA

Background: Improved survival of adult patients with acute lymphoblastic leukemia (ALL) has emerged from identifying new prognostic markers. Overexpression of FAT1 cadherin has been implicated in leukemogenesis and predicts disease outcome. The aim of this study is to detect the expression of FAT1 cadherin in adult patients with ALL and its impact on prognosis and disease outcome. Subjects and Methods: Fifty two adult patients with ALL as well as ten hematologically normal subjects as a control group, were enrolled for determination of FAT1 cadherin mRNA by quantitative real time polymerase chain reaction. Results: FAT1 cadherin mRNA was high (? 0.01 copies/ml) in 27/52 (52%) of ALL patients. In the control group, FAT1 expression was low (< 0.01 copies /ml). FAT1 expression was significantly correlated with high total leucocytic count as well as unfavorable cytogenetic analysis. Regarding the clinical outcome of ALL patients, out of 25 patients with low FAT1 expression, 20 (80%) showed continuous complete remission (CCR), while 5 (20%) failed to achieve CCR (relapsed or died). On the other hand, among 27 patients with high FAT1 expression, 11 (41%) showed CCR, while 16(59%) failed to achieve CCR (relapsed or died), revealing a highly significant relationship between high FAT1 expression and poor clinical outcome (P < 0.001). Conclusion: FAT1 is expressed on leukemic cells in adult patients with ALL, but not on normal cells, its expression is associated with poor clinical outcome. These data make FAT1 a promising candidate for disease monitoring, risk stratification as well as development of targeted therapies.