Background: A variety of cytokines have been demonstrated to regulate the growth, survival, differentiation and apoptosis of leukemia cells. However, little is known about the expression of cytokine receptors on acute myeloid leukemia (AML) cells and their prognostic relevance.
Aim: We aimed to determine the prevalence and the prognostic significance of various cytokine receptor expressions in adult AML.
Methods: Using flow cytometry, we quantitatively examined the expression of interleukin-2 receptor α-chain (IL-2Rα), IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, common β (βc), γc, granulocyte-macrophage colony-stimulating factor (GM-CSF)Rα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 on cells from 676 adult patients with AML, and evaluated their prognostic relevance.
Results: All cytokine receptors examined were expressed to various degrees, whereas the levels of IL-3Rα, GM-CSFRα, IL-2Rα, γc, c-kit, and G-CSFR exhibited a wide spectrum of more than 10,000 sites/cell. In younger patients (less than 60 years), high levels of IL-3Rα, GM-CSFRα, and IL-2Rα correlated with low responses to conventional chemotherapy, but only IL-2Rα was associated with a shorter overall survival (OS). Multivariate analysis including other prognostic markers, CD4, CD7, and CD11b revealed IL-2Rα as an independent adverse factor for OS, and its expression status also remained prognostic within the ctogenetic-risk stratification for AML which is currently recognized as the most powerful risk information for AML. Incorporation of IL-2Rα status into this system could clearly separate the intermediate-risk patients into additionally two prognostic subgroups. Older patients (over 60 years) did not have any such findings.
Conclusions: Among various cytokine receptors we examined, expression of IL-2Rα was solely correlated with a poor outcome in patients with AML (less than 60 years), and its prognosice value was independent of other adverse factors. Assessment of IL-2Rα should be added to current risk evaluation system as a valuable phenotypic marker to provide better prognostication of AML.