Adaptor molecules expression in normal lymphopoiesis and in childhood leukemia

Abstract

Transmembrane adaptor proteins are key mediators of antigen receptor signaling in lymphocytes. By influencing proliferation and differentiation, these molecules might play a role in ethiopathogenesis of acute lymphoblastic leukemia (ALL). The aim of this study was to characterize expression of PAG, LAT, NTAL and LIME adaptors at the mRNA and protein levels in normal B- and T-precursors. Moreover, diagnostic samples of childhood ALL cases were analyzed. During normal lymphocyte development, some adaptors show significant dynamics (gradual decrease of NTAL and increase of LAT and LIME during the T-cell maturation, decrease of PAG in B-precursors, high levels of LIME in peripheral B-lymphocytes). Analysis of childhood ALL samples revealed that in B-cell precursor ALL, the TEL/AML1 subgroup have unique adaptor profile compared to other leukemias. Moreover, NTAL expression separates T lineage leukemias into two subgroups with good and poor response to initial prednisone therapy showing prognostic impact of this molecule in T-ALL.