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¹ Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan
² Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan
³ Department of Hematology, National Kyushu Cancer Center, Fukuoka 811-1395, Japan
⁴ Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
⁵ Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115

CORRESPONDENCE Koichi Akashi: akashi{at}med.kyushu-u.ac.jp

To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872–11877) was composed of the interleukin 5 receptor chain⁺ (IL-5R⁺) and IL-5R^– fractions, and the former was the hEoP. The IL-5R⁺CD34⁺CD38⁺IL-3R⁺CD45RA^– hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5R^– hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an "IL-5R–negative" criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.

Abbreviations used: BaP, basophil lineage-committed progenitor; CCR3, CC chemokine receptor 3; CMP, common myeloid progenitor; EoP, eosinophil lineage-committed progenitor; Epo, erythropoietin; EPX, eosinophil peroxidase; FOG-1, friend of GATA-1; GMP, granulocyte/macrophage progenitor; HDC, histidine decarboxylase; HES, hypereosinophilic syndrome; HSC, hematopoietic stem cell; IL-5R, IL-5R chain; MegE, megakaryocyte/erythroid; MEP, megakaryocyte/erythrocyte progenitor; MNC, mononuclear cell; MPO, myeloperoxidase; MPP, multipotent progenitor; PMN, polymorphonuclear cell; SCF, stem cell factor; Tpo, thrombopoietin.

© 2009 Mori et al.
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