| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The colony-promoting activities of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), recombinant granulocyte colony-stimulating factor (rG-CSF), and recombinant interleukin 3 on primary and secondary colony formation by blast progenitors (leukemic colony-forming units;L-CFU) from patients with acute myeloblastic leukemia (AML) were examined using blast colony assay and compared to colony promotion stimulated by pytohemaggulutinin-stimulated leukocyte-conditioned medium (PHA-LCM). Recombinant GM-CSF stimulated blast colonies in 13 out of 20 cases examined. The magnitude of stimulation by rM-CSFf varied significantly according to the type of AML, but in general was lower than that of PHA-LCM. Blast cells in type M1 did not form any colonies with rGM-CSF, and type M4 blasts formed fairy large numbers of colonies, though slightly less than those stimulated by PHA-LCM. Recombinant G-CSF stimulated blast colonies in only 5 out of 21 cases, 3 of them being type M2. The n
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umber of cases responding to rG-CSF was significantly smaller than that responding to rGM-CSF, and the magnitude of stimulation was minimal. Recombinant G-CSF is not likely to play an essential role in the proliferation of leukemic blasts of most types. Recombinant IL-3 stimulated blast colonies in 12 out of 27 cases examined, however, the magnitude of stimulation by rIL-3 was significantly lower than that by PHA-LCM. No preferential growth of blast colonies was observed according to the AML subtype. Frequency and magnutude of growth stimulation by rIL-3 were not significantly different to those seen by rGM-CSF or RG-CSF. Previous exposure to rGM-CSF, rG-CSF or rIL-3 did not alter the self-renewal capacity, cellular phenotype, and morphology of colony cells, indicating that the direction and the degree of differentiation of L-CFU stimulated by rGM-CSF, rG-CSF or rIL-3 were not different from those stimulated with PHA-LCM. Simulateneous addition of rIL-3 with rGM-CSF or rG-CSF revealed variable results; a simple additive effect in a half of cases studied, and a significantly higher or lower values in the remaining cases. These results may indicate heterogenous responsiveness to CSFs on leukemic blast cells. Less
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