Patients with acute myeloid leukemia can be subclassified based on the constitutive cytokine release of the leukemic cells; the possible clinical relevance and the importance of cellular iron metabolism

Abstract

ABSTRACTObjective: Acute myeloid leukaemia (AML) is a heterogeneous malignancy; we studied how the constitutive cytokine release by the AML cells varies among patients.Methods: We investigated the constitutive release of 28 mediators during in vitro culture for 79 consecutive patients.Results: Constitutive cytokine release profiles differed among patients, and hierarchical clustering identified three subsets with high, intermediate and low release, respectively. The high-release subset showed high levels of most mediators, usually monocytic differentiation as well as altered mRNA expression of proteins involved in intracellular iron homeostasis and molecular trafficking; this subset also included 4 out of 6 patients with inv(16). Spontaneous in vitro apoptosis did not differ among the subsets. For the high-release patients, cytokines were released both by CD34+ and CD34− cells. The mRNA and released protein levels showed statistically significant correlations only for eleven of the cytokines. The overall survival after intensive anti-leukemic therapy was significantly higher for high-release compared with low-release patients. Pharmacological targeting of iron metabolism (iron chelation, transferrin receptor blocking) altered the cytokine release profile.Conclusions: Subclassification of AML patients based on the constitutive cytokine release may be clinically relevant and a part of a low-risk (i.e. chemosensitive) AML cell phenotype.