2018 Fiscal Year Annual Research Report
The mechanism of CML leukemia progenitor cells eradication uncovered by Sipa1 deficiency
| Project/Area Number |
18F18406
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
湊 長博 京都大学, 医学研究科, 理事 (40137716)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
XU YAN 京都大学, 医学(系)研究科(研究院), 外国人特別研究員
|
|---|
| Project Period (FY) |
2018-10-12 – 2021-03-31
|
| Keywords | Bcr-Abl mutation / Colon caner / Sipa1 |
|---|
| Outline of Annual Research Achievements |
1. Sipa1-deficient mice resisted the CML initiating cells expressing drug-resistant mutant Bcr-Abl.
T315I / E225V Bcr-Abl mutant cell lines, which are highly stronger resistant to imatinib than wild-type Bcr-Abl, were used to perform the intravenous injection experiment. Spia1-/- mice also rejected T315I / E225V CML- initiating cells.
2. Various tumor cell lines were used to verify whether the potent anti-cancer immunity can be unleashed for other types of tumors. Primary results indicated that Spia1-/- mice may also resisted the colon cancer cells (MC38) in an orthotopic model.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We first dissect the molecular mechanisms on how Sipa1-deficiency lead to the effective interaction of T cells and MSCs in tumor microenvironment for CML eradication. Then in resent research we verified Sipa1 deficient mice also showed resistance to the HPCs expressing drug-resistant mutant Bcr-Abl as well. And this resistance immune mechanism may also suit for other cancer models such as colon cancer cells (MC38) which suggest that Sipa1 may be a promising target for cancer immunotherapy. So we think current research is progressing as expected.
|
| Strategy for Future Research Activity |
1. We will confirm our data on the cancer cells with potential immunogenicity and possibly cancer stem cells, such as colon and lung cancer models.
2. We want to investigate the relationship between CML-resistance with cellular senescence.
3. We will start to prepare the cell system to analyze the intracellular function of Sipa1 regulating cell motility. We will particularly focus on the identification of the Sipa1-interacting molecules involved in the inhibition of cell motility for the possible targeting Sipa1 function with low molecular weight compounds.
|
