title: TGF beta 1 and IL-4 have opposing effects on the proliferation of chronic phase chronic myeloid leukaemic cells stimulated by G-CSF in vitro.
abstract: The effects of transforming growth factor beta 1 (TGF beta 1) have been studied in vitro on the clonogenicity of haemopoietic progenitor cells (CFU-CML) from 14 patients with chronic myeloid leukaemia (CML) in chronic phase and 13 normal donors. In 14/14 patients with CML, 5 ng of TGF beta 1/dish decreased CFU-CML-formation in cultures stimulated with 15 ng of granulocyte colony-stimulating factor (G-CSF)/dish (p < 0.0005) and in 13/14 patients TGF beta 1 reduced CFU-CML-formation induced by G-CSF in combination with 5 ng of recombinant human interleukin-4 (rhIL-4)/dish (p < 0.005). In 10/14 samples the number of CFU-CML were reduced to levels lower than in cultures containing G-CSF alone (p < 0.01). In contrast, TGF beta 1 had no significant inhibitory effect on the G-CSF-directed proliferation of normal donor mononuclear cells (MNC) either alone or in combination with rhIL-4. RhIL-4 increased G-CSF-induced colony formation in 13/14 CML samples (p < 0.001), but did not have the same effect in the normal donor samples. The in vitro clonogenicity of CML peripheral blood MNC stimulated with 15 ng of G-CSF could not be correlated with the white cell count or the percentage of CD34+ cells at diagnosis.
authors.affiliation: Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: P
authors.initials: P
authors.lastname: Mahendra
authors.forename: R K
authors.initials: RK
authors.lastname: Barfoot
authors.forename: J B
authors.initials: JB
authors.lastname: Bell
authors.forename: J G
authors.initials: JG
authors.lastname: Treleaven
authors.forename: R L
authors.initials: RL
authors.lastname: Powles
authors.forename: J L
authors.initials: JL
authors.lastname: Millar
authors.forename: B C
authors.initials: BC
authors.lastname: Millar
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D002455:Cell Division / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D016212:Transforming Growth Factor beta; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4