Defects of Granulopoiesis in Patients with Severe Congenital Neutropenia

Nakamura Kazuhiro

Kobayashi Masao

Konishi Nakao

Kawaguchi Hiroshi

Miyagawa Shin-ichiro

Sato Takashi

Katoh Osamu

Ueda Kazuhiro

Hiroshima Journal of Medical Sciences

[PISSN] 0018-2052

[EISSN] 2433-7668

[NCID] AA00664312

To confirm the abnormalities of primitive myeloid progenitor cells in patients withsevere congenital neutropenia (SCN), we studied their responsiveness to hematopoieticfactors including granulocyte colony-stimulating factor (G-CSF). In all SCN patientsstudied no abnormalities of granulocyte colony-stimulating factor receptor (G-CSFR) genewere detected by polymerase chain reaction-single-strand conformation polymorphism analysisand sequence analysis. A flow cytometric analysis of bone marrow cells based on theexpression of CD34, Kit receptor, and G-CSFR demonstrated a reduced frequency ofCD34+/Kit+/G-CSFR+ cells in patients with SCN. The granulocyte/macrophage (GM)-colonyformation of CD34+/Kit+/G-CSFR+ cells in patients was markedly decreased at allconcentrations of G-CSF in serum-deprived semisolid culture. The responsiveness ofCD34+/Kit+/G-CSFR+ cells in patients showed a reduced response to the combination of stemcell factor, the ligand for flk2/flt3, and interleukin-3 with or without G-CSF inserum-deprived semisolid and liquid suspension cultures. In contrast, no difference in theresponsiveness of CD34+/Kit+/G-CSFR- cells was noted between SCN patients and normalsubjects. The bone marrow cells from a patient who underwent bone marrow transplantationshowed a restoration of both the reduced frequency and the decreased level of GM-colonyformation of CD34+/Kit+/G-CSFR+ cells. These results demonstrate that the presence ofqualitative and quantitative abnormalities of primitive myeloid progenitor cells expressingG-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN.

Granulocyte colony-stimulating factor

Granulocyte colony-stimulating factor receptor

Fluorescence activated cell sorting

Severe congenital neutropenia

Medical sciences [ 490 ]

eng

Hiroshima University Medical Press

[Created] 2006-03-21

[ISSN] 0018-2052

[NCID] AA00664312