title: Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia: high CD40 and CD11a expression correlates with poor prognosis.
abstract: The expression of adhesion and co-stimulatory molecules, and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression of these molecules in 99 AML patients using monoclonal antibodies and flow cytometry, and correlated the expression with French-American-British (FAB) classification and survival. The following molecules were studied: the co-stimulatory molecules CD80, CD86 and CD40; the adhesion molecules CD11a-c, CD31, CD43, CD50, CD54, CD102, CD58 and CD62L; the chemokine receptor CXCR4; and the death receptors TNFR1 and TNFR2 and FAS. The expression of all molecules was significantly higher in the M4/M5 FAB subgroups except for CD80, CD43, CD54 and CD62L. The AML M3 subgroup had a significant lower expression of CD11a (P = 0.02) and CD11c (P = 0.03). Five-year survival was significantly shorter in cases of high CD40 expression [> 20% positive cells, relative risk (RR) 2.56, P = 0.02] or high CD11a expression (> 80% positive cells, RR 2.6, P = 0.03). This effect was most prominently present in the AML M4/M5 FAB subgroups. We conclude that the expression levels of adhesion and co-stimulatory molecules, CXCR4 and apoptosis-receptors are predominantly FAB subtype-related with high CD40 and CD11a expression as poor prognostic factors.
authors.affiliation: Laboratory of Experimental Haematology, Department of Haematology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: R E
authors.initials: RE
authors.lastname: Brouwer
authors.forename: J
authors.initials: J
authors.lastname: Hoefnagel
authors.forename: B
authors.initials: B
authors.lastname: Borger van Der Burg
authors.forename: I
authors.initials: I
authors.lastname: Jedema
authors.forename: K H
authors.initials: KH
authors.lastname: Zwinderman
authors.forename: I C
authors.initials: IC
authors.lastname: Starrenburg
authors.forename: H C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: R M
authors.initials: RM
authors.lastname: Barge
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015996:Survival Rate; D019014:fas Receptor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D019718:Receptors, CXCR4; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor