Characterization of cytokine, growth factor receptor, costimulatory and adhesion molecule expression patterns of bone...

Relapse of childhood acute lymphoblastic leukaemia (ALL) comprises a leading 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 from 10 children with relapsed B cell precursor ALL. The gene and protein expression of essential haematopoietic growth factors (IL-2, IL-4, IL-7, IL-10, IL-15, IFN-gamma, G-CSFR), their corresponding receptors as well as the expression pattern of adhesion molecules (ICAM-1, CD58) and costimulatory proteins (CD40, CD40L, B7.1, B7.2, CD28, MHC-I and II) was analyzed by RT-PCR and flow cytometry. Constitutive gene expression was found for IL-7, IL-10, IL-15 and IFN-gamma and their corresponding receptors. Flow-cytometric analysis showed that IL-10R, IL-7Ralpha, IL-4Ralpha and the gamma(c)chain are constitutively expressed, and that some cells bear the G-CSFR. IL-10 and IL-15 protein-producing leukaemic cells were easily detectable. The neoplastic cells mainly lack B7.1, and ICAM-1 is mostly decreased. Furthermore, high CD40, and, surprisingly, CD40L expression could be found. These studies 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 conventional adhesion and costimulatory molecules might represent an effective mechanism of escape of immune surveillance in relapsed ALL.