MétaCan
Menu
Back to cohort
Record W1839791560 · doi:10.1158/0008-5472.can-14-2676

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death

2015· article· en· W1839791560 on OpenAlexaff
Eric A. Lee, Leonard Angka, Sarah-Grace Rota, Thomas Hanlon, Andrew Mitchell, Rose Hurren, Xiao Ming Wang, Marcela Gronda, Ezel Boyacı, Barbara Bojko, Mark D. Minden, Shrivani Sriskanthadevan, Alessandro Datti, Jeffery L. Wrana, Andrea N. Edginton, Janusz Pawliszyn, Jamie W. Joseph, Joe Quadrilatero, Aaron D. Schimmer, Paul A. Spagnuolo

Bibliographic record

VenueCancer Research · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Hypoxia, and Metabolism
Canadian institutionsMount Sinai HospitalOntario Institute for Cancer ResearchUniversity of Waterloo
Fundersnot available
KeywordsMyeloid leukemiaMitochondrionStem cellLeukemiaProgenitor cellHaematopoiesisApoptosisBiologyProgrammed cell deathCellViability assayCancer researchCytotoxicityHematopoietic stem cellCell biologyCytotoxic T cellMyeloidBiochemistryChemistryImmunologyIn vitro

Abstract

fetched live from OpenAlex

Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic investigations indicated that cytotoxicity relied on mitochondrial localization, as cells lacking functional mitochondria or CPT1, the enzyme that facilitates mitochondria lipid transport, were insensitive to avocatin B. Furthermore, avocatin B inhibited fatty acid oxidation and decreased NADPH levels, resulting in ROS-dependent leukemia cell death characterized by the release of mitochondrial proteins, apoptosis-inducing factor, and cytochrome c. This study reveals a novel strategy for selective leukemia cell eradication based on a specific difference in mitochondrial function.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.183
Threshold uncertainty score0.542

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.053
GPT teacher head0.353
Teacher spread0.300 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations176
Published2015
Admission routes1
Has abstractyes

Explore more

Same venueCancer ResearchSame topicCancer, Hypoxia, and MetabolismFrench-language works237,207