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.
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.
Mahendra
P
P
Institute of Cancer Research, Sutton, Surrey, UK.
Barfoot
R K
RK
Bell
J B
JB
Treleaven
J G
JG
Powles
R L
RL
Millar
J L
JL
Millar
B C
BC
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*
D015703:Antigens, CD; D018952:Antigens, CD34; D016212:Transforming Growth Factor beta; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4