Evidence map›Paper›PMID 41468895›Full record

ArticleCell reports. Medicine2026

CDK4/6 inhibition overcomes venetoclax resistance mechanisms with enhanced combination activity in acute myeloid leukemia.

Melissa L Stewart, Jessica Gibbs, Kevin Watanabe-Smith, Ariel Nguyen, Isabel Kenna, Karina Thiel-Klare, Andy Kaempf, Daniel Bottomly, Stephen E Kurtz, Christopher A Eide and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Melissa L StewartDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Jessica GibbsDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Kevin Watanabe-SmithDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Ariel NguyenDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Isabel KennaDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Karina Thiel-KlareDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Andy KaempfKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Biostatistics Shared Resource, Oregon Health & Science University, Portland, OR 97239, USA.
Daniel BottomlyKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Stephen E KurtzDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Christopher A EideDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Nicola LongDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Jennifer N SaultzDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Luca SaxDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Ariane HuangDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Shannon K McWeeneyKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR, USA; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Bill H ChangKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Division of Hematology and Oncology, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
Jeffrey W TynerDivision of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. Electronic address: tynerj@ohsu.edu.

Funding

Tumor Intrinsic and Microenvironmental Mechanisms Driving Drug Combination Efficacy and Resistance in AMLU54CA224019 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Tothu Q Vu · 2017 to 2026
$13.9M
Mechanisms of venetoclax combination activity in acute myeloid leukemiaR01CA262758 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Stephen E Kurtz, Jeffrey Wallace Tyner · 2021 to 2026
$2.1M
NCI NIH HHS R01 CA262758NCI NIH HHS U54 CA224019
6 · The paper itself

Abstract

Venetoclax (ven) combined with azacytadine is a widely used therapy for acute myeloid leukemia (AML). However, most patients develop resistance. To identify more effective combinations, we analyze 302 AML patient samples and find ven plus palbociclib (ven+palbo), a cyclin dependent kinase (CDK)4/6 inhibitor, to be highly effective. Ven+palbo shows synergistic activity in AML cell lines and patient-derived xenograft mouse models. Patient samples exhibiting a synergistic response to ven+palbo show downregulation of genes involved in protein synthesis. Genome-wide (CRISPR) screening shows that loss of translational genes uniquely confers sensitivity to ven but not to ven+palbo. AML cells exposed to ven exhibit an adaptive increase of protein synthesis that is overcome by ven+palbo through regulation of translational machinery. Additionally, ven+palbo mitigates resistance mechanisms observed with single-agent ven (BAX loss) and palbo (RB1 loss). Finally, we identify the loss of IKZF1 as a mechanism of resistance to ven+palbo and show that targeting AXL is effective in IKZF1-mutated AML.

Indexed as

Bridged Bicyclo Compounds, HeterocyclicCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Drug Resistance, NeoplasmLeukemia, Myeloid, AcuteSulfonamidesAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorDrug SynergismHumansMiceMice, Inbred NODPiperazinesProtein Kinase InhibitorsPyridinesBridged Bicyclo Compounds, HeterocyclicCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6palbociclibPiperazinesProtein Kinase InhibitorsPyridinesSulfonamidesvenetoclaxcell statemonocyticprogenitortargeted therapy

Identifiers

PMID41468895
PMCPMC12866115

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.