title: Granulopoietic differentiation in long-term bone marrow cultures from children with congenital neutropenia.
abstract: The capacity of granulopoietic precursor cells (CFU-GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short-term colony assays and long-term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU-GM, which displayed an appropriate response to various sources of GM-CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long-term bone marrow cultures from three patients, despite a normal production of CFU-GM, myeloblasts, and promyelocytes during the 5-6 week culture period. Thus, in these patients, the characteristic "block" in granulocytic maturation observed in vivo was reproduced in vitro in long-term cultures. Granulocytic differentiation proceeded normally in long-term cultures from the two other patients, thus indicating heterogeneity in the expression of the defect. These results might indicate abnormal interactions between stromal and hematopoietic cells in long-term marrow cultures from some patients with congenital neutropenia. Furthermore, our results showed some correlation between the granulocytic defect in vitro and the clinical outcome in vivo.
authors.affiliation: Laboratoire d'Hématologie, Hôpital Bicêtre, France.
authors.forename: L
authors.initials: L
authors.lastname: Coulombel
authors.forename: N
authors.initials: N
authors.lastname: Morardet
authors.forename: F
authors.initials: F
authors.lastname: Veber
authors.forename: C
authors.initials: C
authors.lastname: Leroy
authors.forename: F
authors.initials: F
authors.lastname: Mielot
authors.forename: A
authors.initials: A
authors.lastname: Fisher
authors.forename: F
authors.initials: F
authors.lastname: Teillet-Thiebaud
authors.forename: G
authors.initials: G
authors.lastname: Tchernia
authors.forename: C
authors.initials: C
authors.lastname: Griscelli
authors.forename: C
authors.initials: C
authors.lastname: Parmentier
mesh_terms: D000380:Agranulocytosis / Q000151:congenital*; D001853:Bone Marrow / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D005260:Female; D006098:Granulocytes / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007223:Infant; D008264:Macrophages / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000097:blood / Q000151:congenital* / Q000473:pathology; D013997:Time Factors