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Regulatory abnormalities in the marrow of patients with myelodysplastic syndromes
Author(s) -
Merchav Shoshana,
Nagler Ar,
FleischerKurtz Gila,
Tatarsky Ilana
Publication year - 1989
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.1365-2141.1989.tb00246.x
Subject(s) - progenitor cell , bone marrow , haematopoiesis , myelodysplastic syndromes , biology , immunology , granulocyte colony stimulating factor , stem cell , granulocyte , myeloid , cancer research , interleukin 3 , medicine , microbiology and biotechnology , t cell , chemotherapy , immune system , antigen presenting cell
Summary Regulation of haemopoiesis in the marrow of patients with myelodysplastic syndromes (MDS) was evaluated by assaying (1) the production of haemopoietic regulators acting upon multipotent and committed progenitors by MDS marrow cells, and (2) the responsiveness of MDS marrow progenitors to stimulation with granulocyte colony‐stimulating factor (G‐CSF). The levels of multipotent progenitor cell colony‐stimulating activity (CFU‐GEMM CSA ) in 7 d bone marrow‐conditioned medium (BMCM) from MDS patients were markedly reduced as compared to controls. MDS BMCM also exhibited reduced levels of burst‐promoting activity (BPA) for primitive erythroid (BFU‐E) progenitors. Both CFU‐GEMM CSA and BPA detected in BMCM were completely neutralized by antibodies directed against interleukin‐3. MDS BMCM exhibited markedly reduced levels of murine‐active CSA. This activity was partially neutralized by anti‐CSF‐1 antibodies. Levels of regulators in BMCM of refractory anaemia (RA), sideroblastic anaemia, RA with excess blasts, and chronic myelomonocytic leukaemia were virtually the same. CFU‐GEMM and BFU‐E growth in MDS marrow ( n = 9) was markedly reduced. A 5‐fold saturating dose of G‐CSF induced an approximately 2‐fold increase in CFU‐GEMM in four of eight MDS and a 1.5‐fold increase of BFU‐E in five of nine MDS, but not in control ( n = 5) marrow cell cultures. Impaired haemopoiesis in MDS marrow may be related to abnormalities both in regulator production by marrow accessory cells and in regulator responsiveness of multipotent and committed progenitors.