title: Abnormalities of primitive myeloid progenitor cells expressing granulocyte colony-stimulating factor receptor in patients with severe congenital neutropenia.
abstract: To define the basis for faulty granulopoiesis in patients with severe congenital neutropenia (SCN), the expression of granulocyte colony-stimulating factor receptor (G-CSFR) in primitive myeloid progenitor cells and their responsiveness to hematopoietic factors were studied. Flow cytometric analysis of bone marrow cells based on the expression of CD34, Kit receptor, and G-CSFR demonstrated a reduced frequency of CD34(+)/Kit(+)/ G-CSFR(+) cells in patients with SCN. The granulocyte-macrophage colony formation of CD34(+)/Kit(+)/G-CSFR(+) cells in patients was markedly decreased in response to G-CSF alone and to the combination of stem cell factor, the ligand for flk2/flt3, and IL-3 with or without G-CSF in serum-deprived semisolid culture. In contrast, no difference in the responsiveness of CD34(+)/Kit(+)/G-CSFR(-) cells was noted between patients with SCN and subjects without SCN. These results demonstrate that the presence of qualitative and quantitative abnormalities of primitive myeloid progenitor cells expressing G-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN. (Blood. 2000;96:4366-4369)
authors: Department of Pediatrics, School of Medicine, Hiroshima University, Hiroshima, Japan.
authors: K
authors: K
authors: Nakamura
authors: M
authors: M
authors: Kobayashi
authors: N
authors: N
authors: Konishi
authors: H
authors: H
authors: Kawaguchi
authors: S
authors: S
authors: Miyagawa
authors: T
authors: T
authors: Sato
authors: H
authors: H
authors: Toyoda
authors: Y
authors: Y
authors: Komada
authors: S
authors: S
authors: Kojima
authors: O
authors: O
authors: Katoh
authors: K
authors: K
authors: Ueda
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002999:Clone Cells; D016895:Culture Media, Serum-Free; D004357:Drug Synergism; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007239:Infections / Q000209:etiology; D007377:Interleukin-3 / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009503:Neutropenia / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012008:Recurrence; D019089:Stem Cell Factor / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D007377:Interleukin-3; D008565:Membrane Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit