title: Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor α-Chain (CD25) Expression Predicts a Poor Prognosis.
abstract: A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor α-chain (IL-2Rα, also known as CD25), IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, the common β-chain (βc), γc, granulocyte-macrophage colony-stimulating factor (GM-CSF)Rα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3Rα, GM-CSFRα, IL-2Rα, γc, c-kit, and G-CSFR exhibited a wide spectrum of ≥10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFRα and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2Rα in non-M3 patients. Elevated levels of IL-3Rα, GM-CSFRα, and IL-2Rα correlated with leukocytosis. In patients ≤60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2Rα was associated with a shorter overall survival. By incorporating IL-2Rα status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2Rα as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2Rα alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ≤60 years old.
authors.affiliation: Cancer Center, Mie University Hospital, Tsu, Japan; Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakase
authors.affiliation: Department of Internal Medicine, Japan Baptist Hospital, Kyoto, Japan; Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Kita
authors.affiliation: Fourth Department of Internal Medicine, Hiroshima Red Cross and Atomic-Bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Kyo
authors.affiliation: First Department of Internal Medicine, Fukui University School of Medicine, Fukui, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Internal Medicine, Suzuka Kaisei Hospital, Suzuka, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Tanaka
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
mesh_terms: D000328:Adult; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012306:Risk
chemical_list: D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit