| RRC ID |
87967
|
| 著者 |
Liu Q, Chen L, Atkinson JM, Claxton DF, Wang HG.
|
| タイトル |
Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model.
|
| ジャーナル |
Cell Death Dis
|
| Abstract |
Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9.
|
| 巻・号 |
7(9)
|
| ページ |
e2361
|
| 公開日 |
2016-9-8
|
| DOI |
10.1038/cddis.2016.264
|
| PII |
cddis2016264
|
| PMID |
27607576
|
| PMC |
PMC5059867
|
| MeSH |
Animals
Autophagy / immunology*
Autophagy-Related Protein 5 / deficiency
Autophagy-Related Protein 5 / genetics
Autophagy-Related Protein 5 / immunology*
Bone Marrow Cells / immunology
Bone Marrow Cells / metabolism
Bone Marrow Cells / pathology
Bone Marrow Transplantation / methods*
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / immunology
Cell Transformation, Neoplastic / pathology
Disease Models, Animal
Gene Deletion
Gene Expression Regulation, Leukemic*
Humans
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / immunology*
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / therapy
Lysosomes / immunology
Lysosomes / metabolism
Mice
Mice, Inbred C57BL
Neoplastic Stem Cells / immunology*
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / immunology*
Signal Transduction
Survival Analysis
|
| リソース情報 |
| 実験動物マウス |
RBRC02975 |
