2023 Fiscal Year Final Research Report
Mechanism of drug resistance acquired after chemotherapy in IDH1-NPM1 mutant AML
| Project/Area Number |
20K17377
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 54010:Hematology and medical oncology-related
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2024-03-31
|
| Keywords | 急性骨髄性白血病 / 化学療法抵抗性 / 疾患モデルマウス / IDH1 / NPM1 |
|---|
| Outline of Final Research Achievements |
We stratify NPM1-mutant AML as favorable risk, unless it is concurrent with other gene lesions suggesting poor prognosis. But, it sometimes relapses soon after it reaches complete remission by chemotherapy, and its long-term survival still needs to be improved. We treated transplant Idh1-Npm1 double knock-in AML model mice with anthracycline and/or cytarabine, which are commonly used in clinic for remission induction chemotherapy. We observed survival elongation in mice treated with combination of anthracycline and cytarabine, but no significant efficacy in mice treated with each single agent. We collected AML cells from the chemo-treated mice in which AML was reduced by chemotherapy once but soon expanding, and will analyze them in order to unveil the mechanism by which AML acquires resistance against chemotherapy,
|
| Free Research Field |
血液内科学
|
| Academic Significance and Societal Importance of the Research Achievements |
Idh1-Npm1変異ダブルノックインAML移植マウスモデルに対するin vivo治療実験により、アントラサイクリン＋シタラビンによる併用化学療法が、各薬剤単剤による治療より優れていることが示された。同AML細胞へのin vitroでの薬剤処理実験でもシタラビンよりアントラサイクリンの感受性が良好であることも示唆された。同AML細胞にとってはアントラサイクリンがKey drugかもしれない可能性が示唆され、さらなる検証が必要である。AML細胞が有している遺伝子変異によって薬剤感受性が大きく異なる可能性があり、サブタイプに特異的に治療を検証する重要性が改めて考えられた。
|
