|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1991 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1990 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Leukemic cells from 34 cases of acute myeloid leukemia (AML), 16 cases of chronic myeloid leukemia (CML; 10 blast crisis and 6 chronic-phase cases), 5 cases of myeloproliferative disorders (MPD), 4 cases of chronic myelomonocytic leukemia (CMML) were studied for growth responsiveness to rhG-CSF, rhGM-CSF, rhIL-3, M-CSF, and for ability of in vitro cytokine production including G-CSF, GM-CSF, M-CSF, IL-1beta, IL-6, and TNFalpha. Findings of these studies are summarized as follows:
(1) Almost all AML cells responded to either rhG-CSF or rhGM-CSF by increased DNA synthesis. (2) There was a direct correlation between growth responsiveness to rhG-CSF and that to rhIL-3. (3) None of 59 cases but one AML (M2) responded to M-CSF by increased DNA synthesis. (4) These leukemia cells frequently released immunoreactive cytokines in culture media (G-CSF 33%, GM-CSF 38%, IL-1beta 33%, IL-6 69%, TNFalpha 78% of cases respectively). (5) There was a direct correlation between production of GM-CSF and that of IL-1beta. (6) In vitro autocrine growth was observed in 4 cases of AML, in which G-CSF and/or GM-CSF were autocrine growth factors. (7) In 3 of these 4 autocrine cases, G-CSF or GM-CSF was detected in the patient sera suggesting that autocrine growth might also take place in vivo. (8) Day three ^3H-thymidine uptake into DNA of leukemic cells directly correlated to their survival length in liquid culture, which tended to be lengthened by rhGM-CSF but not by rhG-CSF. (9) A CMML-derived tumor cell line OMK-91 was established, which was found to express CD14, IIb/IIIa platelet associated antigen, HLA-DR, and to produce M-CSF, G-CSF, and IL-1bata. (10) Thirteen Blymphoblastoid cell lines were established from these patients.