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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4086-4092.
Prepublished online as a Blood First Edition Paper on August 30, 2005; DOI 10.1182/blood-2005-03-1072.


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Submitted March 16, 2005
Accepted August 3, 2005

Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia

David C Taussig, Daniel J Pearce, Catherine Simpson, Ama Z Rohatiner, Andrew T Lister, Gavin Kelly, Jennifer L Luongo, Gwenn-ael H Danet-Desnoyers, and Dominique Bonnet*

Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom
Division of Haematological Oncology, St Bartholomew's Hospital, London, United Kingdom
Fluorescence Activated Cell Sorting Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom
Computational Genome Analysis Laboratory, Cancer Research UK, London Research InstituteUniversity of Pennsylvania, School of Medicine, London, United Kingdom
Department of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, USA
Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom; Department of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, USA

* Corresponding author; email: dominique.bonnet{at}cancer.org.uk.

Human hematopoietic stem cells (HSCs) are generally thought to lack the markers expressed by differentiated blood cells, the lineage specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that the well-established myeloid markers CD33, CD13 and/or CD123 are expressed on human long term repopulating cells from cord blood and bone marrow. In addition, we demonstrate that NOD/SCID leukemia initiating cells (SL-IC) were restricted to the CD33+ fraction in 11 of 12 acute myeloid leukemia (AML) samples studied, indicating that leukemic stem cells (LSCs) express this antigen. This study changes our view of HSCs and the process of differentiation. Furthermore, based on the phenotypic similarity of HSCs and LSCs, our data provide support for the hypothesis that AML derives from a HSC. Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen targeted therapies, given the potential for HSC killing.


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