Open AccessIn vitro enhancement of erythropoiesis by steel factor in diamond‐blackfan anemia and treatment of other congenital cytopenias with recombinant interleukin 3/granulocyte‐macrophage colony stimulating factor
Author(s) -
Sieff Colin,
Guinan Eva
Publication year - 1993
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.5530110819
Subject(s) - diamond–blackfan anemia , bone marrow failure , erythropoietin , granulocyte macrophage colony stimulating factor , bone marrow , granulocyte colony stimulating factor , erythropoiesis , biology , immunology , anemia , medicine , stem cell factor , thrombopoietin , myelodysplastic syndromes , cytokine , haematopoiesis , endocrinology , stem cell , chemotherapy , ribosome , rna , biochemistry , genetics , gene
Recombinant cytokines were used to investigate the pathophysiology of Diamond‐Blackfan anemia (DBA) and to treat patients with Fanconi's anemia (FA) and amegakaryocytic thrombocytopenic purpura (AMD. We compared the erythroid burst forming units (BFU‐E) colony growth of six DBA patients with four normal controls. BFU‐E showed erythropoietin (Epo) dose dependence in all patients, although colony numbers were reduced in comparison with normals. The number and size of BFU‐E were increased with the addition to Epo of interleukin 3 (IL‐3) or Steel factor (SF), but IL‐3 + SF was not synergistic SF increased the nonadherent cell production in DBA long‐term bone marrow cultures, and stromal cells from DBA patients showed normal SF mRNA transcripts. These data suggest that SF is not involved in the pathogenesis of DBA, although it may be useful in treatment A small group of patients with FA and bone marrow failure were treated with daily s.c. granulocyte‐macrophage colony stimulating factor (GM‐CSF). Toxicity was minimal, and the majority of the patients responded with significant, sustained increase in neutrophils. Multilineage response was rare. GM‐CSF may thus be palliative in patients with FA. Five patients with AMT were treated with IL‐3 or IL‐3 followed by GM‐CSF in a Phase I/II study. There was minimal toxicity, and IL‐3, but not GM‐CSF, resulted in improved platelet counts in two patients and decreased platelet transfusion requirements in the other three. Prolonged IL‐3 treatment resulted in platelet increases in two of the latter patients. Thus, IL‐3 may contribute to the treatment of patients with AMT.