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A Novel Five-Transmembrane Hematopoietic Stem Cell Antigen: Isolation, Characterization, and Molecular Cloning

Sheri Miraglia, Wayne Godfrey, Amy H. Yin, Kristin Atkins, Roger Warnke, Jeannine T. Holden, Robert A. Bray, Edmund K. Waller, and David W. Buck

From AmCell Corp, Sunnyvale; Department of Microbiology, University of California, San Francisco; Department of Pathology, Stanford University Medical Center, Stanford, CA; Department of Pathology, and Department of Medicine, Division of Hematology-Oncology, Emory University School of Medicine, Atlanta, GA.

Phenotypic analysis of hematopoietic stem and progenitor cells (HSCs) has been an invaluable tool in defining the biology of stem cell populations. We have recently described the production of AC133, a monoclonal antibody (MoAb) that binds to a novel cell surface antigen present on a CD34bright subset of human HSCs. This antigen is a glycosylated protein with a molecular weight of 120 kD. Here, we report the molecular cloning of a cDNA encoding this antigen and show that it does not share homology with any previously described hematopoietic or other cell surface antigen(s). The AC133 polypeptide has a predicted size of 97 kD and contains five-transmembrane (5-TM) domains with an extracellular N-terminus and a cytoplasmic C-terminus. Whereas the expression of tetraspan (4-TM) and 7-TM molecules is well documented on mature and immature hematopoietic cells and leukocytes, this 5-TM type of structure containing two large (255-amino acid [aa] and 290-aa) extracellular loops is unique and does not share sequence homology with any known multi-TM family members. Expression of this protein appears limited to bone marrow in normal tissue by immunohistochemical staining; however, Northern analysis suggests that the mRNA transcript is present in a variety of tissues such as the kidney, pancreas, placenta, and fetal liver. The AC133 antigen is also expressed on subsets of CD34+ leukemias, suggesting that it may be an important early marker for HSCs, as well as the first described member of a new class of TM receptors.

Blood, Vol. 90 No. 12 (December 15), 1997: pp. 5013-5021
© 1997 by The American Society of Hematology.


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AC133 Antigen Expression Is Not Restricted to Acute Myeloid Leukemia Blasts But Is Also Found on Acute Lymphoid Leukemia Blasts and on a Subset of CD34+ B-Cell Precursors
Blood, July 15, 1999; 94(2): 832 - 833.
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P. A. Horn, H. Tesch, P. Staib, D. Kube, V. Diehl, D. Voliotis, and C. Schoch
Expression of AC133, a Novel Hematopoietic Precursor Antigen, on Acute Myeloid Leukemia Cells
Blood, February 15, 1999; 93(4): 1435 - 1437.
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D Corbeil, K Roper, M. Hannah, A Hellwig, and W. Huttner
Selective localization of the polytopic membrane protein prominin in microvilli of epithelial cells - a combination of apical sorting and retention in plasma membrane protrusions
J. Cell Sci., January 4, 1999; 112(7): 1023 - 1033.
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K. Kratz-Albers, M. Zuhlsdorf, R. Leo, W. E. Berdel, T. Buchner, and H. Serve
Expression of AC133, a Novel Stem Cell Marker, on Human Leukemic Blasts Lacking CD34- Antigen and on a Human CD34+ Leukemic Cell Line: MUTZ-2
Blood, December 1, 1998; 92(11): 4485 - 4487.
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E. A. de Wynter, D. Buck, C. Hart, R. Heywood, L.H. Coutinho, A. Clayton, J.A. Rafferty, D. Burt, G. Guenechea, J. A. Bueren, et al.
CD34+AC133+ Cells Isolated from Cord Blood are Highly Enriched in Long-Term Culture-Initiating Cells, NOD/SCID-Repopulating Cells and Dendritic Cell Progenitors
Stem Cells, November 1, 1998; 16(6): 387 - 396.
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S. Miraglia, W. Godfrey, and D. Buck
A Response to AC133 Hematopoietic Stem Cell Antigen: Human Homologue of Mouse Kidney Prominin or Distinct Member of a Novel Protein Family?
Blood, June 1, 1998; 91(11): 4390 - 4391.
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D. Corbeil, K. Roper, A. Weigmann, and W. B. Huttner
AC133 Hematopoietic Stem Cell Antigen: Human Homologue of Mouse Kidney Prominin or Distinct Member of a Novel Protein Family?
Blood, April 1, 1998; 91(7): 2625 - 2626.
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A. H. Yin, S. Miraglia, E. D. Zanjani, G. Almeida-Porada, M. Ogawa, A. G. Leary, J. Olweus, J. Kearney, and D. W. Buck
AC133, a Novel Marker for Human Hematopoietic Stem and Progenitor Cells
Blood, December 15, 1997; 90(12): 5002 - 5012.
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