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Constitutional Aplastic Anaemia: Defective Haematopoietic Stem Cell Growth in Vitro
Author(s) -
Saunders E. F.,
Freedman M. H.
Publication year - 1978
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1978.tb03664.x
Subject(s) - haematopoiesis , stem cell , aplastic anemia , bone marrow , biology , erythropoiesis , immunology , stromal cell , erythropoietin , bone marrow failure , andrology , cancer research , medicine , anemia , endocrinology , microbiology and biotechnology
S ummary . . Seven children with constitutional aplastic anaemia (one dyskeratosis congenita, one constitutional type without anomalies, five classical Fanconi's anaemia) were studied to define the pathogenesis of the marrow failure. Haematopoiesis was assessed by assay of granulocytic (CFU‐C) and erythrocytic (CFU‐E) colonies in vitro . Numbers of CFU‐C were profoundly reduced or absent in marrow cultures from all patients (range 0‐5 CFU‐C/10 5 , control range 15‐106/10 5 ). Numbers of CFU‐E were also strikingly reduced or absent (range 0‐2 CFU‐E/10 5 , control range 31‐317/10 5 ) with one exception. No CFU‐C could be grown from peripheral blood. Incubation of the patients' sera with control marrow failed to demonstrate inhibition of CFU‐C, colony stimulating activity (CSA), CFU‐E or erythropoietin (EPO). The peripheral blood lymphocytes from these patients in co‐culture experiments failed to inhibit CFU‐C or CFU‐E growth from control marrow. Aplastic marrow co‐cultured with control marrow also failed to demonstrate cellular inhibition. CSA production from patients’peripheral blood leucocytes averaged 93% of the activity of a standard control CSA, suggesting normal granulopoietic stimulation. The data indicate a problem early in haematopoiesis. Although a defect in the stromal microenvironment cannot be excluded, it is possible the defect is intrinsic to the haematopoietic stem cells, either an absence or marked reduction in stem cells, or a failure of stem cells to grow colonies in Vitro .