Interaction of transforming growth factor-beta 1 with hemopoietic growth factors in the regulation of human normal and leukemic myelopoiesis.
We studied the effect of transforming growth factor-beta 1 (TGF-beta 1) on the growth of normal and chronic myeloid leukemia (CML) granulo-monopoietic progenitors (CFU-GM) and erythroid progenitors (BFU-E) of different origins and degrees of maturation. In the presence of the supernatant of the 5637 cell line, used as a source of growth factors, TGF-beta 1 stimulates the growth of day-7 CFU-GM from Ficoll-isolated normal bone marrow cells. Maximum stimulation (172% of controls) is observed with 2.5 ng/ml TGF-beta. The results with a highly enriched progenitor cell population stimulated by recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant granulocyte-macrophage CSF (rGM-CSF) were similar, suggesting a direct effect of TGF-beta 1 on hemopoietic progenitors. In contrast to this stimulatory effect of TGF-beta 1 on normal day-7 bone marrow CFU-GM, TGF-beta 1 does not affect the growth of day-14 CFU-GM. The growth of normal bone marrow BFU-E is strongly inhibited. In the majority of cases (11/15) of CML, bone marrow day-7 CFU-GM growth is inhibited by TGF-beta 1. In few cases (4/15) leukemic progenitors respond to TGF-beta 1 as normal cells. TGF-beta 1 always inhibits the growth of day-14 bone marrow CFU-GM from CML patients.
Dipartimento di Scienze Biomediche ed Oncologia Umana dell'Università, Torino, Italy.
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M
Aglietta
A
A
Stacchini
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A
Severino
F
F
Sanavio
M L
ML
Ferrando
W
W
Piacibello
D001853:Bone Marrow / Q000502:physiology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004347:Drug Interactions; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D003115:Colony-Stimulating Factors; D015291:Transforming Growth Factors