Evidence map›Paper›PMID 42362999›Full record

ArticleNature cancer2026

Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.

Xin He, Lei Zhang, Yang Li, Song-Bai Liu, Zheng Li, Haojie Dong, Genevieve E Baker, Le Xuan Truong Nguyen, Wei Chen, Jinhui Wang and 23 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cancer, 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. Review
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

33 authors.

Xin He *Department of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Lei Zhang *Department of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Yang Li *Department of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Song-Bai Liu *Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, China.ORCID http://orcid.org/0000-0002-3920-1032
Zheng Li *National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Haojie DongDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Genevieve E BakerDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Le Xuan Truong NguyenDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-5464-0861
Wei ChenIntegrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Jinhui WangIntegrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-3499-4336
Zhilian JiaDepartment of Computational and Quantitative Medicine & Systems Biology, City of Hope Medical Center, Duarte, CA, USA.
Xiyuan LuDepartment of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.
Yi-Chun LinCollege of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
Zunsong HuDepartment of Computational and Quantitative Medicine & Systems Biology, City of Hope Medical Center, Duarte, CA, USA.
Umesh Prasad YadavDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Meng LiuDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-5040-4156
Lianjun ZhangDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-5285-0088
Zhenhua ChenDepartment of Computational and Quantitative Medicine & Systems Biology, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-1381-0235
Xiwei WuIntegrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Jianjun ChenDepartment of Computational and Quantitative Medicine & Systems Biology, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-3749-2902
Chun-Wei ChenDepartment of Computational and Quantitative Medicine & Systems Biology, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-8737-6830
Stefano TizianiDepartment of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-7230-0307
Weidong HuDepartment of Immunology and Theranostics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-3911-5262
Ya-Huei KuoDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-2595-0419
Sheng-Li XueNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.ORCID http://orcid.org/0000-0003-4609-616X
Yong ZhangDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-3132-8557
Min LiDivision of Biostatistics, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Yaoqiu ZhuCollege of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
Guido MarcucciDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-3983-5908
Zhaohui GuDepartment of Computational and Quantitative Medicine & Systems Biology, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-1581-1327
J Jefferson P PerryDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-9889-3502
Yun Lyna LuoCollege of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.ORCID http://orcid.org/0000-0003-3581-754X
Ling LiDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA. lingli@coh.org.ORCID http://orcid.org/0000-0001-7568-939X

Funding

Targeting Protein Arginine Methyltransferases to Eradicate Acute Myeloid LeukemiaR01CA279595 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LING LI · 2024 to 2026
$2.1M
Targeting AMP Synthesis to Overcome Resistance to BH3 Mimetics in Acute Myeloid LeukemiaR01CA292893 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LING LI · 2025 to 2026
$1.4M
NCI NIH HHS R01 CA279595NCI NIH HHS R01 CA292893
6 · The paper itself

Abstract

De novo purine synthesis is required to maintain tumor growth; however, its impact on therapy resistance remains unclear. Here, through a dynamic BH3-priming-based CRISPR screen, we found that deletion of ADSS2, which encodes the adenylosuccinate synthase 2 enzyme essential for adenosine monophosphate (AMP) synthesis, re-sensitizes drug-resistant acute myeloid leukemia cells to venetoclax and a myeloid cell leukemia-1 (MCL1) inhibitor. Single-cell sequencing analysis of patient-derived xenograft samples revealed a positive association of high ADSS2 activity in TP53-mutant cells with poor responsiveness to venetoclax. We developed an ADSS2 antagonist, which synergized with BH3 mimetics to promote apoptosis in preclinical models. Mechanistically, sensitization mediated by ADSS2 targeting correlated with downregulated AMP-activated protein kinase activity, which in resistant cells promotes mitophagy to eliminate damaged mitochondria after BH3 mimetic treatment. These data show that AMP synthesis promotes BH3 mimetic resistance and that combining ADSS2 targeting with BH3 mimetics represents a promising anti-cancer approach.

Indexed as

Adenosine MonophosphateLeukemia, Myeloid, AcuteAnimalsApoptosisBridged Bicyclo Compounds, HeterocyclicCell Line, TumorDrug Resistance, NeoplasmHumansMicePeptide FragmentsProto-Oncogene ProteinsSulfonamidesXenograft Model Antitumor AssaysAdenosine MonophosphateBax protein (53-86)Bridged Bicyclo Compounds, HeterocyclicPeptide FragmentsProto-Oncogene ProteinsSulfonamidesvenetoclax

Identifiers

PMID42362999

What OpenQuestion holds

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Registered trials

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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.