title: The characterization of chemokine production and chemokine receptor expression reveals possible functional cross-talks in AML blasts with monocytic differentiation.
abstract: 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.
  
  
  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 (MO-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.
authors.affiliation: University Division of Clinical Immunology and Hematology, Ospedale Mauriziano Umberto I, Turin, Italy. alex.cignetti@ircc.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cignetti
authors.forename: Antonella
authors.initials: A
authors.lastname: Vallario
authors.forename: Ilaria
authors.initials: I
authors.lastname: Roato
authors.forename: Paola
authors.initials: P
authors.lastname: Circosta
authors.forename: Giuliana
authors.initials: G
authors.lastname: Strola
authors.forename: Cristina
authors.initials: C
authors.lastname: Scielzo
authors.forename: Bernardino
authors.initials: B
authors.lastname: Allione
authors.forename: Lucia
authors.initials: L
authors.lastname: Garetto
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis; D054418:Chemokine CCL20; D018925:Chemokines / Q000032:analysis / Q000096:biosynthesis*; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D020239:Receptor Cross-Talk; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis / Q000096:biosynthesis*
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine