Characterization of cytokine, growth factor receptor, costimulatory and adhesion molecule expression patterns of bone marrow blasts in relapsed childhood B cell precursor ALL

Relapse of childhood acute lymphoblastic leukaemia (ALL) comprises a leadin g challenge of investigation. Characterization of leukaemic cells regarding their potency to express growth factors and surface molecules can provide insight into their aberrant biology. Thus, we analyzed bone marrow blasts f rom 10 children with relapsed B cell precursor ALL. The gene and protein ex pression of essential haematopoietic growth factors (IL-2, IL-4, IL-7, IL-1 0, IL-15, IFN-gamma, G-CSFR), their corresponding receptors as well as the expression pattern of adhesion molecules (ICAM-1, CD58) and costimulatory p roteins (CD40, CD40L, B7.1, B7.2, CD28, MHC-I and II) was analyzed by RT-PC R and flow cytometry, Constitutive gene expression was found for IL-7, IL-I O, IL-15 and IFN-gamma and their corresponding receptors, Flow-cytometric a nalysis showed that IL-10R, IL-7R alpha, IL-4R alpha and the gamma (c), cha in are constitutively expressed, and that some cells bear the G-CSFR, IL-10 and IL-15 protein-producing leukaemic cells were easily detectable. The ne oplastic cells mainly lack B7.1, and ICAM-1 is mostly decreased. Furthermor e, high CD40, and, surprisingly, CD40L expression could be found. These stu dies show that ALL cells are likely to be sensitive to many growth factors and some factors are produced by the neoplastic cell itself. The secretion of IL-10 by leukaemic cells, and the absence or downregulation of conventio nal adhesion and costimulatory molecules might represent an effective mecha nism of escape of immune surveillance in relapsed ALL. (C) 2001 Academic Pr ess.