Adaptor molecules PAG, NTAL and LAT in physiological lymphocyte precursors and in childhood leukaemia
Abstract
Transmembrane adaptor proteins do not posses an enzymatic or kinase function, but they mediate signal transmission from cell surface to the nucleus. In animal model, changes in PAG adaptor molecule expression induce a leukaemia-like phenotype.
In this study, adaptor molecules PAG, LAT, NTAL were analysed in physiological lymphocyte precursors and in 75 diagnostic samples of childhood acute lymphoblastic leukaemia (ALL). The expression status was assessed at mRNA level (using real-time quantitative reverse-transcriptase polymerase chain reaction) and at protein level (using flow cytometry).
During a physiological maturation of lymphocyte precursors an expression status of some adaptors shows significant dynamics among distinct maturation stages. Among different ALL subgroups different adaptor molecules expression dynamics can be seen, particularly in TEL/AML1 patients displaying a unique profile of expression.
NTAL level at the diagnosis of T-ALL has a prognostic impact predicting good or poor response to initial corticosteroid treatment. This observation was confirmed in in vitro assay - after incubation with corticoids a percentage of surviving cells is higher in wild-type T-ALL cell line compared to the same cells with transfected NTAL gene.