Imaging dynamic mTORC1 pathway activity in vivo reveals marked shifts that support time-specific inhibitor therapy in AML
What this study shows
Fluorescent probes imaged in the bone marrow of live mice show mTORC1 activity in AML cells falls as the disease progresses but is high at the moment of maximal chemotherapy response, where it is induced rather than selected; inhibiting mTORC1 at that time improved killing of AML cells.
Abstract
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Acute myeloid leukemia (AML) is a high remission, high relapse fatal blood cancer. Although mTORC1 is a master regulator of cell proliferation and survival, its inhibitors have not performed well as AML treatments. To uncover the dynamics of mTORC1 activity in vivo, fluorescent probes are developed to track single cell proliferation, apoptosis and mTORC1 activity of AML cells in the bone marrow of live animals and to quantify these activities in the context of microanatomical localization and intra-tumoral heterogeneity.
Read the full abstract on PubMed →At a glance
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| Evidence type | A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse AML model; intravital imaging of bone marrow with fluorescent probes); the code names the system studied -- animal work can be rigorous and still not be human data. |
| Study type | 4 - Animal Study |
| Model system | Mouse AML model; intravital imaging of bone marrow with fluorescent probes |
| Journal | Nature Communications |
| Year | 2021 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1038/s41467-020-20491-8 · PMID 33431855 · Free full text (PMC7801403) |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
People in the Atlas
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Hematology researcher who trained at the Institute of Medical Science in Tokyo and in David Scadden's lab at Massachusetts General Hospital, where he imaged mTORC1 activity in leukemia cells inside living mice
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Stem cell and leukaemia biologist whose lab imaged mTORC1 activity in live mice and showed that well-timed mTORC1 inhibition kills more leukaemia cells
More: 10 other authors
No profile yet: Mercier F, Kato H, Jung Y, McDonald TO, Spencer JA, Mazzola MC, van Gastel N, Lin CP, Michor F, Kitamura T
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Chemotherapy; timed mTORC1 inhibition |
| Target | mTORC1 (AML cells in vivo) |
| Model | Mouse |
| Effect | mTORC1 activity in AML shifts over the course of disease and treatment; timed inhibition works better |
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