Subclassification of patients with acute myelogenous leukemia based on chemokine responsiveness and constitutive chemokine release by their leukemic cells.

摘要: Background and Objectives Chemokines are soluble mediators involved in angiogenesis, cellular growth control immunomodulation. In the present study we investigated effects of various chemokines on proliferation acute myelogenous leukemia (AML) cells constitutive chemokine release by primary AML cells.Design Methods Native human derived from 68 consecutive patients were cultured vitro. We cell (3H-thymidine incorporation, colony formation), receptor expression, chemotaxis normal peripheral blood mononuclear cells.Results Exogenous usually did not have any effect blast absence hematopoietic factors, but when investigating factor-dependent (interleukin 3 + granulocyte-macrophage colony-stimulating factor stem factor) suspension cultures following patient subsets identified: (i) whose showed chemokine-induced enhancement (8 patients); (ii) divergent (15 (iii) no (most patients). These differ but, compared to CD34− cells, CD34+ higher expression several receptors. also increased clonogenic first subset patients. Furthermore, a broad profile was detected for most patients, clusters could be CCL2-4/CXCL1/8, CCL5/CXCL9-11 (possibly CCL23) CCL13/17/22/24/CXCL5 CXCL6). Only CCL2-4/CXCL1/8 cluster significant correlations between corresponding mRNA levels NFκB levels/activation. The immunocompetent without observed decreased.Interpretation Conclusions Differences responsiveness as well contribute heterogeneity AML. Patients with can classified into distinct according their profile.