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Record W4416447989 · doi:10.1093/jimmun/vkaf283.2715

Inhibition of cGAS as a novel treatment for acute myeloid leukemia 9292

2025· article· en· W4416447989 on OpenAlexaff
Xin Zhang

Bibliographic record

VenueThe Journal of Immunology · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
Topicinterferon and immune responses
Canadian institutionsUniversity Health Network
Fundersnot available
KeywordsMyeloid leukemiaHaematopoiesisCytarabineLeukemiaMyeloidImmune systemInterferonInnate immune system

Abstract

fetched live from OpenAlex

Abstract Description Acute myeloid leukemia (AML) is an aggressive blood cancer featuring clonal expansion of malignant myeloid progenitors. Current treatment of AML remains a combination of cytarabine and anthracycline that causes dsDNA breaks. Although this regimen initially reduces leukemic cells, almost 65% of patients suffer a relapse. Thus, a better understanding of the molecular pathogenesis of AML is needed to devise more effective therapeutic strategies. cGAS functions in immune responses by sensing double-stranded DNA or mitochondrial DNA in the cytosol of a damaged cell. cGAS binding to such DNA triggers a cell cycle-dependent response in which “Stimulator of Interferon Genes” (STING) mediates the expression of inflammatory genes, including IFN-1, IL6 and TNFα. Hematopoietic stem cells in this inflammatory environment are biased to undergo myeloid differentiation. Our preliminary data indicating that, in an adoptive transfer mouse model of AML, animals that received cGAS-/-AML cells didn’t develop full leukemia even at 1yr post-transplant. Thus, leukemic cells may need cell-autonomous cGAS to expand, and cGAS may be pro-tumorigenic in AML. Moreover, mRNA levels of cGAS, STING, IL-6 and TNFα are altered in samples from AML patients, suggesting cGAS-related inflammation may be persistent in human leukemias.Indeed, most AML cells exhibit elevated DNA damage or mutations, which could lead to ds/mt DNA release and excessive cGAS activation. cGAS may be a novel therapeutic target for AML. Funding Sources Pre-clinical AstraZeneca Grant Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.014
GPT teacher head0.283
Teacher spread0.269 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2025
Admission routes1
Has abstractyes

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