TY - JOUR
T1 - Interleukin (IL)-15 induces survival and proliferation of the growth factor-dependent acute myeloid leukemia M-07e through the IL-2 receptor β/γ
AU - Meazza, Raffaella
AU - Basso, Stefania
AU - Gaggero, Alessia
AU - Detotero, Daniela
AU - Trentin, Livio
AU - Pereno, Raffaele
AU - Azzarone, Bruno
AU - Ferrini, Silvano
PY - 1998
Y1 - 1998
N2 - We have analyzed the effects of IL-15, a growth factor with IL-2-like properties produced by dendritic and stromal cells, on 3 GM-CSF/IL-3- dependent AML cell lines: M-07e, UT-7 and TF-I. M-07e cells proliferated in response to IL-15, while UT-7 and TF-I cells failed to respond. In addition, IL-15 supported long-term proliferation of M-07e cells, thus allowing selection of a subline (M-07SB), which displayed an enhanced sensitivity to IL-15. M-07e and M-07SB cells undergo apoptosis following 48-hr growth factor (GM-CSF or IL-15) starvation, as detected by cytofluorimetric analysis and DNA laddering. IL-15 (20 ng/ml) prevented apoptosis in both cell lines. M- 07e and M-07SB expressed IL-2Rβ, IL-2Rγ, Jak-1 and Jak-3 mRNA, while IL- 15Rα mRNA was undetectable. In contrast, IL-15Rα was expressed in UT-7 and TF-I cells, which lacked expression of IL-2Rβ mRNA and, in the case of UT- 7, also of Jak-3 mRNA. Accordingly, surface IL-2Rβ protein was identified only in M-07e and M-07SB cells, by indirect immunofluorescence, while no expression of IL-2Rα and IL- 15Rα was detected. Anti-IL-2Rβ antibodies (10 μg/ml) efficiently blocked (90% inhibition) the proliferation and the anti- apoptotic effect induced by IL-15, while anti-GM-CSFRα antibodies had no effect. Anti-IL-2Rγ antibodies were less efficient at proliferation inhibition but synergized with suboptimal concentrations of anti-IL-2Rβ antibodies. Our data suggest a role of IL-15 as an anti-apoptotic and mitogenic growth factor for a subset of myeloid leukemias expressing a functional I L-2Rβ/γ complex.
AB - We have analyzed the effects of IL-15, a growth factor with IL-2-like properties produced by dendritic and stromal cells, on 3 GM-CSF/IL-3- dependent AML cell lines: M-07e, UT-7 and TF-I. M-07e cells proliferated in response to IL-15, while UT-7 and TF-I cells failed to respond. In addition, IL-15 supported long-term proliferation of M-07e cells, thus allowing selection of a subline (M-07SB), which displayed an enhanced sensitivity to IL-15. M-07e and M-07SB cells undergo apoptosis following 48-hr growth factor (GM-CSF or IL-15) starvation, as detected by cytofluorimetric analysis and DNA laddering. IL-15 (20 ng/ml) prevented apoptosis in both cell lines. M- 07e and M-07SB expressed IL-2Rβ, IL-2Rγ, Jak-1 and Jak-3 mRNA, while IL- 15Rα mRNA was undetectable. In contrast, IL-15Rα was expressed in UT-7 and TF-I cells, which lacked expression of IL-2Rβ mRNA and, in the case of UT- 7, also of Jak-3 mRNA. Accordingly, surface IL-2Rβ protein was identified only in M-07e and M-07SB cells, by indirect immunofluorescence, while no expression of IL-2Rα and IL- 15Rα was detected. Anti-IL-2Rβ antibodies (10 μg/ml) efficiently blocked (90% inhibition) the proliferation and the anti- apoptotic effect induced by IL-15, while anti-GM-CSFRα antibodies had no effect. Anti-IL-2Rγ antibodies were less efficient at proliferation inhibition but synergized with suboptimal concentrations of anti-IL-2Rβ antibodies. Our data suggest a role of IL-15 as an anti-apoptotic and mitogenic growth factor for a subset of myeloid leukemias expressing a functional I L-2Rβ/γ complex.
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U2 - 10.1002/(SICI)1097-0215(19981005)78:2<189::AID-IJC12>3.0.CO;2-6
DO - 10.1002/(SICI)1097-0215(19981005)78:2<189::AID-IJC12>3.0.CO;2-6
M3 - Article
C2 - 9754651
AN - SCOPUS:0031659389
VL - 78
SP - 189
EP - 195
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -