Impairment of GM‐CSF production in myelodysplastic syndromes

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Abstract
Summary. In this study we evaluated the production of granulocyte/macrophage‐colony stimulating factor (GM‐CSF), interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) by enriched bone marrow (BM) macrophages in 15 patients affected by myelodysplasia and 20 normal BM donors. The presence of GM‐CSF, IL‐6 and TNF‐α in the culture supernatants of BM macrophages was detectable only after stimulation with lipopolysaccharide (LPS), whereas no differences were present in the amount of IL‐6 and TNF‐α between myelodysplastic patients and normal controls, GM‐CSF production appeared eight‐fold reduced in BM macrophage culture supernatants from myelodysplastic patients with respect to normal controls. After further experiments, we concluded that the impaired release of GM‐CSF by BM macrophages could not be due to a different production kinetic in myelodysplastic patients. Moreover, the number of multipotent (CFU‐GEMM), granulocyte/macrophage (CFU‐GM) and erythroid (BFU‐E) progenitors was significantly impaired in myelodysplastic patients. In conclusion, we demonstrated that the production of GM‐CSF by purified adherent cells from MDS patients is markedly impaired in spite of the peripheral blood cytopenia. This selective defect in GM‐CSF production, along with an intrinsic defect of haematopoietic progenitor cells, might contribute to the impairment of haematopoiesis always observed in myelodysplastic patients.