The clinical and prognostic significance of FIS1, SPI1, PDCD7 and Ang2 expression levels in acute myeloid leukemia.

OBJECTIVES: The marked heterogeneity of acute myeloid leukemia (AML) renders precisely predicting patient prognosis extremely difficult. Genetic alterations, fusions and mutations, may result in misexpression of key genes in AML. We aimed to investigate the expression patterns of 4 novel genes; FIS1, SPI1, PDCD7 and Ang2 to determine their potential prognostic role in AML patients.

METHODS: Bone marrow mononuclear cells were analyzed for of FIS1, SPI1, PDCD7 and Ang2 expression levels by real-time quantitative PCR as well as of FLT3/ITD and NPM1 mutations in 100 newly diagnosed cytogenetically normal (CN-AML) patients, and 100 non-malignant controls.

RESULTS: FIS1, SPI1, PDCD7 and Ang2 were significantly overexpressed in CN-AML patients (p < 0.001). Their high expression levels were significantly associated with lower complete remission (CR) rate, shorter relapse-free survival (RFS) and overall survival (OS). On multivariate analysis, high FIS1 expression showed a significant impact on CR response after induction therapy (OR = 88.777, 95% C.I: 2.85-2765.78, p = 0.011) while high PDCD7 appeared to be an independent risk factor for RFS (HR = 5.107, 95% C.I: 1.731-15.066, p = 0.003) and OS (HR = 7.353, 95% C.I: 1.859-29.079, p = 0.004) in CN-AML patients.

CONCLUSIONS: FIS1 and PDCD7 expression are considered independent risk factors and should be integrated into the current AML stratification system.