Background:Numerous cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, the prognostic value of measuring cytokine receptor expression levels in cells from acute myeloid leukemia (AML) patients is not well established.
Aim:We aimed to determine the prevalence and the clinical significance of cytokine receptor expression in adult patients with AML.
Methods:We quantitatively measured expression levels of interleukin-2 receptor α-chain (IL-2Rα, CD25), IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, common β-chain (βc), γc, granulocyte-macrophage colony-atimulating factor (GM-CSF)Rα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130, in cells from 767 adult AML patients by flow cytometry, and then correlated these results with clinical and biological (phenotype and cytogenetics) features of adult AML.
Results:Variable expression levels were observed with all cytokine receptors studied, with the widest ranges observed (≥10,000 sites/cell) with IL-2Rα, IL-3Rα, γc, GM-CSFRα, G-CSFR, and c-kit. In patients ≤60 years old, high levels of IL-2Rα, IL-3Rα, and GM-CSFRα expression correlated with poor responses to intensive chemotherapy, but only IL-2Rα was associated with a shorter overall survival (OS). Multivariate analysis including other prognostic phenotype marker CD4, CD7, and CD11b revealed IL-2Rα as an independent adverse factor for OS, and its expression status improved AML prognostication independent of cytogenetic data which is currently recognized as the most powerful marker for risk classification of adult AML.
Conclusions:Among the various cytokine receptors studied, IL-2Rα expression alone was associated with poor outcomes in patients ≤60 years old, and its prognostic value was independent of other adverse factors. IL-2Rα assessment should be added to current risk evaluation systems as a phenotype marker to provide better prognostication of adult patients with AML