Gamma-interferon interrupts growth stimulation in chronic myelogenous leukemia established by endogenous granulocyte colony-stimulating factor.
We have previously shown that maturing neoplastic cells from patients with stable phase chronic myelogenous leukemia (SP CML) constitutively produce granulocyte colony-stimulating factor (G-CSF) and are also receptive for this molecule. G-CSF functions as an endogenous growth factor in SP CML, and thus is responsible for divisions in maturing leukemic cells leading to an expansion of the compartment of mature cells. In the investigations to be reported below, the effects of various hematopoietic inhibitor molecules on the expression of the G-CSF gene by SP CML bone marrow cells enriched for promyelocytes/myelocytes were examined at the mRNA and protein level. We show that exposure of SP CML bone marrow promyelocytes/myelocytes to recombinant human (rh) interferon (IFN)-gamma but not to rh IFN-alpha, rh tumor necrosis factor (TNF)-alpha, and rh lymphotoxin (LT) leads to downregulation of G-CSF expression and interruption of the G-CSF-mediated endogenous growth stimulation. The action of G-CSF takes place at the posttranscriptional level and involves an acceleration of decay of steady-state levels of G-CSF transcripts in the malignant cell population.
Department of Hematology and Oncology, University of Freiburg Medical Center, F.R.G.
D
D
Riedel
A
A
Lindemann
J
J
Otto
U
U
Brennscheidt
M
M
Lübbert
R
R
Mertelsmann
F
F
Herrmann
D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000378:metabolism / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007370:Interferon Type I; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma