2016 Fiscal Year Final Research Report
Targeting cancer stem cells in chronic myeloid neoplasms
| Project/Area Number |
26461424
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | 骨髄増殖性腫瘍 / 骨髄異形成症候群 / がん幹細胞 / 免疫不全マウス / SIRPA / Kit変異 |
|---|
| Outline of Final Research Achievements |
Cancer stem cells (CSCs) are therapeutic targets and must be eliminated to cure the patients. Howerver ,those cells have not been found yet in MDS/MPN. Immunodeficient mice are widely used to reconstitute human normal hematopoiesis and acute leukemia. Howerever, in these models, significant reconstitution of human erythroid and megakaryocyte lineages has been difficult to achieve. Here, we show that introduction of homozygous KitWv mutation (K) into the C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multilineage reconstitution. The new BRGSK mice showed significantly higher levels of human cell chimerism and myeloid reconstitution for a long-term, as compared to BRGS mice. Strikingly, BRGSK mice displayed robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow.This new xenograft model should be a strong tool to study human hematopoiesis including erythropoiesis and thrombopoiesis.
|
| Free Research Field |
血液内科学
|
