Long-term bone marrow culture in Fanconi's anaemia.
Fanconi's anaemia (FA) is the most common of the constitutional aplastic anaemias; the mechanisms leading to aplasia in this disease are poorly understood. A number of mechanisms have been implicated in the pathogenesis of acquired aplastic anaemia (AA), including a stem cell defect, an immune reaction against haematopoietic cells or defective function of the marrow microenvironment. To investigate the pathophysiology of this disorder we have performed bone marrow colony forming unit-granulocyte macrophage (CFU-GM) assays and long-term bone marrow culture (LTC) in 22 cases of FA compared with 17 cases of acquired AA. Defective in vitro haematopoiesis was observed in all patients with FA, including several cases with normal peripheral blood counts. The mean CFU-GM value for the FA group was approximately 15 times lower than for the normal group. A correlation was seen between CFU-GM and the severity of neutropenia in FA. In LTC an adherent layer formed in all cases of FA; despite this fact CFU-GM were either not generated or rapidly fell to zero in all patients. LTC is a sensitive method for the detection of impaired granulopoiesis in FA and reveals defects in all patients with this disease.
Bone Marrow Transplant Unit, Hôpital Saint Louis, Paris, France.
R
R
Stark
D
D
Thierry
P
P
Richard
E
E
Gluckman
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D003114:Colony-Forming Units Assay; D005199:Fanconi Anemia / Q000473:pathology*; D005260:Female; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D013997:Time Factors