NUCLEAR NF-ATP IS A HALLMARK OF UNSTIMULATED B-CELLS FROM B-CLL PATIENTS

B lymphocytes from the peripheral blood of patients with chronic lymph ocytic leukaemia (CLL) were analysed for the nuclear presence and DNA binding of a panel of transcription factors which are involved in the gene control of lymphoid cells. The following transcription factors we re studied: the Octamer factors Oct-1 and Oct-2, members of the AP-1 f actor family, NF-AT factors, in particular NF-ATp, and members of the Rel/NF-kB family. We show that the constitutive nuclear translocation of NF-ATp, a member of the growing family of NF-AT factors, is a hallm ark of nonstimulated B cells from CLL patients that distinguishes B-CL L cells from 'normal' B lymphocytes. Constitutive nuclear appearance w as also observed for NF-kB2/p52. Constitutive binding of further facto r proteins to DNA, such as JunD, c-Fos and FosB, was detected in sever al patients whereas the localisation and DNA binding of other factors such as c-Jun, RelA/p65 and c-Rel was unaltered. It is remarkable that in B-CLL cells the nuclear appearance and DNA binding of specific tra nscription factors is dramatically affected whereas other members of t he same factor family remained unaltered in these leukaemic cells. It remains to be shown which molecular events lead to the specific 'pre-a ctivation', i.e. constitutive nuclear translocation and DNA binding, o f these members of NF-AT, NF-kB and AP-1 factor families.