| Project/Area Number |
16H06744
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Yamazaki Sho 東京大学, 医学部附属病院, 助教 (00779407)
|
|---|
| Project Period (FY) |
2016-08-26 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 慢性骨髄単球性白血病 / 網羅的遺伝子解析 / 標的治療 / シグナル伝達 / iPS細胞 / オミクス解析 / 血球分化能 / 細胞増殖能 |
|---|
| Outline of Final Research Achievements |
Chronic myelomonocytic leukemia (CMML) is a refractory and recurrent hematopoietic malignancy. We identified SLITRK4 as a causative gene of CMML by using induced pluripotent stem cells (iPSC) from CMML patient-derived leukemic cells. We disrupted SLITRK4 gene in CMML iPSC via CRISPR/Cas9 system, and the production of hematopoietic progenitor cells (HPC) from CMML-iPSC was dramatically attenuated in SLITRK4 dose-dependent manner. In addition, SLITRK4 was knocked down after hematopoietic differentiation from CMML-iPSC and Normal-iPSC, and the number of CMML-HPC-derived colonies was reduced by knockdown of SLITRK4, although Normal-HPC-derived colonies did not change. Next, we performed Gene Ontology Enrichment Analysis and found genes related to cytoskeleton and cell cortex such as SPTA1 and SPTBN1 were highly expressed in CMML-HPC compared to Normal-HPC.
|
