ArticleCancer discovery2023
Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Impact of secondary-type mutations on the prognosis of AML patients with NPM1 mutation: a systematic review and meta-analysis.Annals of hematology · 2025Pooled it
- Trial
- Dynamic genetic and nongenetic RAS-pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.Blood · 2026Article
- Wired to Survive: How AML Cytogenetics Shape Apoptotic Dependence and Venetoclax Resistance.Genes · 2026Review
- Apoptosis gene expression analysis identifies biologically distinct AML clusters and BIK as an independent prognostic marker.Annals of hematology · 2026Article
- Venetoclax for elderly patients with acute myeloid leukaemia unfit for intensive chemotherapy: Prospects, resistance mechanisms and management strategies.Clinical and translational medicine · 2026Review
- Article
- m6A and NuRD complexes regulate monocytic differentiation and resistance to BCL2/BCL2L1 inhibitors in acute myeloid leukemia.Haematologica · 2026Article
- Controversies in the Management of AML in Older Patients: A Canadian Perspective.Current oncology (Toronto, Ont.) · 2026Review
- Genomic Subtype Influences BH3 Mimetic Drug Sensitivity and Synergy with Cytotoxic Chemotherapeutics in T-cell Acute Lymphoblastic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Diving into the transcriptional landscape of leukemic stem cells in acute myeloid leukemia at single-cell resolution.Journal of cancer research and clinical oncology · 2026Review
- TIM-3 in AML: a janus-faced orchestrator of immune exhaustion and leukemic self-renewal.Cancer cell international · 2026Review
- MCL1 inhibition to enhance the efficacy of MYB targeting in pediatric acute myeloid leukemia.Cell death & disease · 2026Article
- TCF3::HLF orchestrates an enhancer-promoter network with activation of MEF2C to promote immature HSC gene expression in leukemia.Science advances · 2026Article
- Synergistic targeting of eIF4A-mediated translation initiation and apoptosis in acute myeloid leukemia.Blood neoplasia · 2026Article
- Bispecific CD37-Siglec6 CAR‑T cells exhibit enhanced anti‑leukemic activity and reduced exhaustion in acute myeloid leukemia xenograft models.Journal of translational medicine · 2026Article
- Review
- CHRNB4-Mediated Neuroactive Signaling Rewiring Drives Adaptive Resistance to BCL-2 Inhibition in Acute Myeloid Leukemia.Cancers · 2026Article
- Therapeutic potential of BH3-mimetics and NK cell-mediated immunotherapy in T-ALL.Cell death & disease · 2026Article
- Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based "Mediators of apoptosis combinatorial score" (MAC-Score) linking the ratio of protein expression of BCL2, BCL-xL, and MCL1 in LSCs. MAC scoring predicts initial response with a positive predictive value of more than 97% associated with increased event-free survival. In summary, combinatorial levels of BCL2 family members in AML-LSCs are a key denominator of response, and MAC scoring reliably predicts patient response to 5-AZA/VEN. SIGNIFICANCE: Venetoclax/azacitidine treatment has become an alternative to standard chemotherapy for patients with AML. However, prediction of response to treatment is hampered by the lack of clinically useful biomarkers. Here, we present easy-to-implement MAC scoring in LSCs as a novel strategy to predict treatment response and facilitate clinical decision-making. This article is highlighted in the In This Issue feature, p. 1275.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.