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The Human ALL-1/MLL/HRX Antigen Is Predominantly Localized in the Nucleus of Resting and Proliferating Peripheral Blood Mononuclear Cells¹

Department of Cytomorphology [M-G. E.] and Institute of Biology [M. N.], Via Porcell 2, University of Cagliari, 09100 Cagliari, Italy; Department of Genetics, Staudtstrasse 5, University of Erlangen-Nürnberg, 91058 Erlangen, Germany [R. G., G. H. F., R. M.]; Institute of Surgical Pathology, Strada Le Grazie, University of Verona, 37134 Verona, Italy [C. S., A. S., S. O.]; and Kimmel Cancer Institute, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [C. M. C.]

The ALL-1 gene is an important regulator of embryonal and hematopoietic development, and structural variants of the human gene generated by chromosomal translocations and other genomic alterations presumably act as oncogenes in the pathogenesis of acute leukemias and other hematological malignancies. Antisera against two different epitopes of the human ALL-1 protein (anti-ALL1-N and anti-ALL1-C) were produced. Both sera revealed indistinguishable patterns of antigen localization in human peripheral blood mononuclear cells (PBMCs). In resting PBMCs, the antigen was distributed in a speckled pattern across the nuclei, with an increased density at the nuclear envelope and the nuclear indentation. In mitotically stimulated PBMCs, the antigen surrounded the condensing chromosomes but did not colocalize with chromatin or the nuclear scaffold. The antigen is considered a marker for a novel nuclear subcompartment, a perichromosomal area termed the "chromsomal envelope." In Western blot experiments, the anti-ALL1-N serum reacted with a polypeptide corresponding to the expected full-length 430-kDa ALL-1 protein. Recombinant proteins representing the AT-hook and zinc binding subdomains of the ALL-1 protein interacted in vitro with a degenerate mixture 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) doublestranded DNA binding mode.

¹ Supported by Research Grants SFB466-C4 (to R. M. and J. G.) and SFB466-C5 (to G. H. F. and R. M.) from the Deutsche Forschungsgemeinschaft; Research Grant Mar/93 from Johannes and Frieda Marohn Stiftung (to R. M. and J. G.); a research grant from the Associazione Italiana Ricerca Cancro to the Istituto Anatomia Patologica of Verona; and a seed grant from the Associazione Italiana Ricerca Cancro (to C. S.). R. M. was supported by a Career Development Award from the Ria Freifrau von Fritsch Stiftung. M-G. E., C. S., and R. G. contributed equally to this work.

² To whom requests for reprints should be addressed, at Department of Genetics, University of Erlangen-Nürnberg, Staudtstrasse 5, D 91058 Erlangen, Germany. Phone: 49-9131-858530; Fax: 49-9131-858626; E-mail: rmarscha@biologie.uni-erlangen.de.

Received 1/22/97. Accepted 3/25/97.

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