The characterization of chemokine production and chemokine receptor expression reveals possible functional cross-talks in AML blasts with monocytic differentiation

Objective. The mechanisms regulating the trafficking of leukemic myeloid blasts are poorly understood. A differential expression of chemokines and chemokine receptors might account for some aspects of the pattern of invasion and accumulation of leukemic cells. We aimed at defining the pattern of chemokine and chemokine receptor expression of acute myeloid leukemia (AML) blasts in comparison with their putative normal cell counterparts. Patients and Methods. Twenty-five cases of AML were analyzed by flow cytometry for the expression of several chemokine receptors and by RT-PCR for the expression of relevant chemokines. For selected chemokines, the production was confirmed by ELISA. AML blasts were also assessed for their migration capacity in response to autologous supernatants and recombinant chemokines. Results. Undifferentiated AML (M0-M1 and some M2) express only CXCR4 on their surface and produce mainly inflammatory chemokines, resembling normal CD34(+) progenitors. More differentiated AML (M4-M5 and some M2) have a more diversified receptor repertoire and, besides CXCR4, express the receptors for inflammatory chemokines and produce both constitutive and inflammatory chemokines, resembling resting and activated monocytes. In particular, M4-M5 blasts produce MCP-1 and MIP-3alpha and also express their specific receptors (CCR2 and, to a lesser extent, CCR6) and migrate in vitro in response to MCP-1 and MIP-3alpha and to their own supernatant. A significant correlation between extramedullary involvement and coexpression of MCP-1/CCR2 was found. Conclusions. These data suggest that chemokines and their receptors segregate within the different FAB subtypes and, by allowing cross-talk among members of the malignant clone, might help to explain some aspects of the pattern of invasion in AML with monocytic differentiation. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc.