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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2062-2070.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-07-2388.
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HEMATOPOIESIS
Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells
Heather M. Bond,
Maria Mesuraca,
Ennio Carbone,
Patrizia Bonelli,
Valter Agosti,
Nicola Amodio,
Gennaro De Rosa,
Massimo Di Nicola,
Alessandro M. Gianni,
Malcolm A. S. Moore,
Akiko Hata,
Michele Grieco,
Giovanni Morrone, and
Salvatore Venuta
From the Department of Experimental and Clinical Medicine "Gaetano Salvatore," University of Catanzaro Magna, Graecia, Italy; Department of Experimental Oncology, National Cancer Institute Fondazione G. Pascale; Clinical Hematology Divison, University of Napoli Federico II, Napoli, Italy; Cristina Gandini Transplantation Unit, Istituto Nazionale Tumori, Milano, Italy; Molecular Cardiology Research Institute, New England Medical Center, Tufts University School of Medicine, Boston, MA; James Ewing Laboratory of Developmental Hematopoiesis and Department of Developmental Biology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Comparison of the gene expression repertoire in human hematopoietic progenitors and mature leukocytes led to identification of a transcript expressed in CD34+cells and undetectable in differentiated cells. Sequencing of the cDNA (termed EHZF: early hematopoietic zinc finger) revealed 30 zinc fingers with 96% homology to mouse Evi3, a recently identified gene associated with the retroviral integration site in AKXD-27 B-cell lymphomas. EHZF and Evi3 share high homology with the transcription cofactor OAZ, implicated in the control of olfactory epithelium and B-lymphocyte differentiation and in the bone morphogenic protein (BMP) signal transduction. Here we show that (1) EHZF expression is abundant in human CD34+ progenitors and declines rapidly during cytokine-driven differentiation; (2) significant mRNA levels are found in most acute myelogenous leukemias; (3) in response to BMPs EHZF complexes SMADs 1 and 4, binds to, and enhances the transcriptional activity of, a BMP2/4 responsive element; (4) EHZF inhibits the transcriptional activity of early B-cell factor (EBF), a transcription factor essential for specification of the B-cell lineage. Taken together, our data suggest that EHZF is likely to play a relevant role in the control of human hematopoiesis and might be implicated in the development of hematopoietic malignancies.

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