| 研究実績の概要 |
We eventually found out that expansion of HOXA9-Sytl1 cells in RAG2-/- or NOD/SCID mice was artifactual, due to MEIS1 gene contamination in our model system.
Recently, the protein Syk (Spleen Tyrosine Kinase) has been shown to be an indirect target of MEIS1 and HOXA9-Syk cells are able to induce leukemia when inoculated into lethally irradiated C57Bl/6 mice.
After having re-established a pure HOXA9-only cell line, we created HOXA9-Syk cells and found that these cells were able to survive and expand up to leukemia onset in non-irradiated immune deficient RAG2-/- or NOD/SCID mice, but not in non-irradiated immune competent C57Bl/6 mice. This result demonstrates that MEIS1 controls the immune evasion of leukemic cells.
In vitro, co-culture of splenic cells with either HOXA9-MEIS1 or HOXA9-Syk cells showed that splenic cells inhibited the proliferation of HOXA9-Syk cells while HOXA9-MEIS1 cells were unaffected. This result could also be observed when using splenocytes from RAG2-/- mice, demonstrating that T and/or B cells are not involved in proliferation inhibition of HOXA9-Syk cells. This result suggested that innate immune cells are responsible for this process.
Importantly, depletion of FcεRI+ cells from splenocytes abrogated the proliferation inhibiting capacity on HOXA9-Syk cells, demonstrating that FcεRI+ cells are responsible for this inhibiting process, while not affecting HOXA9-MEIS1 cells.
The proliferation inhibiting capacity of FcεRI+ cells was mediated through secreted factors since supernatant only was sufficient to suppress proliferation of HOXA9-Syk cells.
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