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Interleukin (IL)‐15 induces survival and proliferation of the growth factor‐dependent acute myeloid leukemia M‐07e through the IL‐2 receptor β/γ
Author(s) -
Meazza Raffaella,
Basso Stefania,
Gaggero Alessia,
Detotero Daniela,
Trentin Livio,
Pereno Raffaele,
Azzarone Bruno,
Ferrini Silvano
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19981005)78:2<189::aid-ijc12>3.0.co;2-6
Subject(s) - cytokine , apoptosis , biology , cancer research , cell growth , cell culture , microbiology and biotechnology , stromal cell , growth factor , receptor , immunology , biochemistry , genetics
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‐1. M‐07e cells proliferated in response to IL‐15, while UT‐7 and TF‐1 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‐1 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 IL‐2Rβ/γ complex. Int. J. Cancer 78:189–195, 1998.© 1998 Wiley‐Liss, Inc.