Long-term bone marrow cultures in Diamond-Blackfan anemia reveal a defect of both granulomacrophage and erythroid progenitors

The hematopoietic defect of Diamond-Blackfan anemia (DBA) results in select ive failure of erythropoiesis, Thus far, it is not known whether this defec t originates from an intrinsic impediment of hematopoietic progenitors to m ove forward along the erythroid pathway or to the impaired capacity of the bone marrow (BM) microenvironment to support proliferation and differentiat ion of hematopoietic cells. Reduced longevity of long-term bone marrow cult ures, the most physiologic in vitro system to study the interactions of hem atopoietic progenitors and hematopoietic microenvironment, is consistent wi th a defect of an early hematopoietic progenitor in DBA, However, stromal a dherent layers from DBA patients generated in a long-term culture system, t he in vitro counterpart of BM microenvironment, did not show evidence of an y morphologic, phenotypic, or functional abnormality. Our major finding was an impaired capacity of enriched CD34(+) BM cell fraction from DBA patient s, cultured in the presence of normal BM stromal cells, to proliferate and differentiate along the erythroid pathway, ii similar impairment was observ ed in some DBA patients along the granulomacrophage pathway. Our result poi nts to an intrinsic defect of a hematopoietic progenitor with bilineage pot ential that is earlier than previously suspected as a relevant pathogenetic mechanism of the disease. The finding of impaired granulopoiesis in some D BA patients underlines the heterogeneity of this rare disorder. (C) 1999 In ternational Society for Experimental Hematology. Published by Elsevier Scie nce Inc.