The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high‐risk myelodysplastic syndromes

Abstract

BACKGROUND.Tumor necrosis factor (TNF)‐α and other cytokines are involved in the pathogenesis of acute myeloid leukemia (AML) and high‐risk myelodysplastic syndromes (MDS), but their prognostic significance in these diseases is unknown. In the current study, the authors assessed the association between serum levels of various cytokines and clinical outcomes in patients with untreated AML or high‐risk MDS.METHODS.Serum levels of TNF‐α, interleukin (IL)‐1 receptor antagonist, IL‐6, IL‐10, and endostatin were measured in patients with AML or high‐risk MDS who presented for treatment at The University of Texas M. D. Anderson Cancer Center from September 1994 through January 2001. Univariate and multivariate analyses were performed to test for correlations with clinical outcomes.RESULTS.Higher TNF‐α levels were found to correlate with poorer performance status; higher leukocyte counts; higher levels of β2‐microglobulin, creatinine, uric acid, and alkaline phosphatase; lower levels of creatinine clearance and albumin; baseline infection; and M4‐M5 AML subtypes. TNF‐α levels <10 pg/mL were associated with higher rates of complete remission (P = .003), survival (P = .0003), and event‐free survival (EFS) (P = .0009). However, on multivariate analyses, TNF‐α level ≥10 pg/mL was not found to be an independent factor predicting clinical outcomes, but became statistically significant when leukocyte count was excluded from the models. The other cytokines were not found to be predictive of clinical outcomes.CONCLUSIONS.High serum TNF‐α level is an adverse prognostic factor for survival and EFS in patients with untreated AML or high‐risk MDS. Cancer 2008. © 2008 American Cancer Society.

Receptor Activator for NF-κB Ligand in Acute Myeloid Leukemia: Expression, Function, and Modulation of NK Cell Immunosurveillance

“…This is in line with findings that many ligands of the TNF family mediate bidirectional signals (33) and with reports that RANKL alters cytokine production of T cells and CLL cells (19,34). The cytokines that we found to be induced by RANKL signaling into AML cells are known to act as autocrine/paracrine growth and survival factors in AML and are, at least in part, associated with development and progression of the disease (35,36). Notably, RANKL signaling did not always induce release of the same cytokines with all RANKL-positive patient samples.…”

“…To this end, primary AML cells of 10 different patients were cultured alone, on isotype control or immobilized RANK-Ig, which enables RANKL multimerization. Subsequent analysis by ELISA revealed that RANKL signaling significantly (all p , 0.05, MannWhitney U test) enhanced the release of TNF, IL-6, IL-8, and IL-10, which are associated with AML pathophysiology (35,36), into the culture supernatants ( Fig. 2A).…”

IL-1 -releasing human acute myeloid leukemia blasts modulate natural killer cell differentiation from CD34+ precursors

“…9 Previous reports showed that serum levels of inflammatory cytokines or chemokines in AML patients may represent a prognostic factor and correlate with the clinical outcome. 10,11 In this context, we have previously shown that IL-8 may accelerate in vitro CD34 + cell differentiation towards CD161 + CD56 + (NK) cells, thus suggesting that cytokines or chemokines, released during an inflammatory process, may influence NK-cell differentiation. 4 In the present study, in order to address the question as to whether AML blasts may affect NK-cell development, we performed co-cultures of umbilical cord blood (UCB)-CD34 + cells in the absence [control (CTR)] or in the presence of fresh leukemia blasts belonging to different FAB categories.…”

Multi-analytical evaluation of serum levels of cytokines and adhesion molecules in patients treated for acute myeloid leukemia using biochip array technology

“…The knowledge gained from multi-analytical determination of cytokines and adhesion molecules could allow better diagnosis and management of hematological malignancies, since cytokines or their receptors may also represent a target for specific anticancer therapy at the molecular level. Recently, some studies reported the possible diagnostic and prognostic use of cytokine levels in newly diagnosed AML and myelodysplastic syndromes [7][8][9] .…”