Expression of Eph A4, Eph B2 and Eph B4 receptors in AML.

Abstract

Eph receptors represent the largest subfamily of receptor tyrosine kinases (RTKs). The up- regulation of Eph receptors has been documented in various solid tumors, where it often correlates with poor prognosis. Their significance in hematologic malignancies is still unclear. This study aimed to investigate the expression of Eph A4, Eph B2, and Eph B4 mRNA in non - M3 AML patients and determine their prognostic significance. Bone marrow samples from 101 newly diagnosed non - M3 AML patients and 26 healthy controls for comparison were quantified by real time reverse transcriptase polymerase chain reaction (RT-PCR), and the comparative cycle threshold (Ct) method was used to determine their relative expression levels to GUS control gene. The results showed that expression of all selected Eph receptors was significantly lower in AML patients comparing to controls. It also differed according to FAB subtypes. The decreased expression levels of Eph A4 were associated with higher leukocytes (p = 0.022) and blast cell counts (p = 0.001), and unfavorable FLT3-ITD mutation. Our study revealed significant correlation between lower EphB2 expression levels, and higher complete remission rate (p = 0.009724) and longer overall survival. Additionally, we found that patients with shorter RFS had decreased EphB4 expression (p = 0.00). In conclusion, the results suggest the prognostic impact of decreased expression levels of some Eph receptors in AML patients.