Immune evasion of AML cells from FceRI+ cells through MEIS1 activity

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K07678
• Research Institution: National Cancer Center Japan
• Principal Investigator: アーノ クズィネ 国立研究開発法人国立がん研究センター, 先端医療開発センター, 特任研究員 (70725621)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Acute Myeloid Leukemia / Meis1 / Immune evasion

Outline of Annual Research Achievements

During this final year, we succeeded in reproducing our previous results using newly created H9M1, H9/DeltaM1 and H9/DeltaM1-SYK clones, ruling out the possibility of an artifactual outcome resulting from random gene integration of our transgenes into leukemia-related gene(s). This result demonstrates that the data have been obtained on a solid experimental basis and strengthens further our scientific purpose.
Thus, we could confirm that H9/DeltaM1-SYK cells are able to induce leukemia in immune deficient RAG2 KO mice, but not in immune competent counterpart C57Bl/6 mice, demonstrating that these cells are eliminated by the immune system.
Furthermore, H9/DeltaM1-SYK cells were able to induce leukemia in basophil-depleted Mcpt8-DTR+ transgenic mice (treated with Diphtheria Toxin), but not in untreated mice, demonstrating that basophils are involved into the elimination of these cells.
These results demonstrate that the transcription factor MEIS1 protects leukemic cells from basophil-mediated elimination.
Additionally, in vitro expansion of H9/DeltaM1-SYK cells was inhibited when co-incubated with splenic cells from C57Bl/6 mice (but not from RAG2 KO mice and Mcpt8-DTR+ transgenic mice treated with Diphtheria Toxin), while H9M1 expansion was poorly affected, confirming our previous results.