THE HUMAN ALL-1 MLL/HRX ANTIGEN IS PREDOMINANTLY LOCALIZED IN THE NUCLEUS OF RESTING AND PROLIFERATING PERIPHERAL-BLOOD MONONUCLEAR-CELLS/

The ALL-1 gene is an important regulator of embryonal and hematopoieti c development, and structural variants of the human gene generated by chromosomal translocations and other genomic alterations presumably ac t as oncogenes in the pathogenesis of acute leukemias and other hemato logical malignancies, Antisera against two different epitopes of the h uman ALL-1 protein (anti-ALL1-N and anti-ALL1-C) were produced, Both s era revealed indistinguishable patterns of antigen localization in hum an peripheral blood mononuclear cells (PBMCs). In resting PBMCs, the a ntigen was distributed in a speckled pattern across the nuclei, with a n increased density at the nuclear envelope and the nuclear indentatio n, In mitotically stimulated PBMCs, the antigen surrounded the condens ing chromosomes hut did not colocalize with chromatin or the nuclear s caffold, The antigen is considered a marker for a novel nuclear subcom partment, a perichromosomal area termed the ''chromosomal envelope.'' In Western blot experiments, the anti-ALL1-N serum reacted with a poly peptide corresponding to the expected full-length 430-kDa ALL-1 protei n, Recombinant proteins representing the AT-hook and zinc binding subd omains of the ALL-1 protein interacted in vitro with a degenerate mixt ure of double-stranded oligodeoxynucleotides. Thus, the ALL-1 protein probably is a DNA-binding protein with both a sequence-unspecific (AT- hook) and a sequence-specific (zinc binding subdomains) double-strande d DNA binding mode.