ArticleLeukemia2022
Targeting leukemia-specific dependence on the de novo purine synthesis pathway.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Glutaredoxin 2 is essential for AML survival through mitochondrial permeability transition pore regulation.Blood · 2026Article
- Identification and Validation of Key Purine Metabolism-Related Genes in Ulcerative Colitis Using Bioinformatics and Machine Learning.Journal of inflammation research · 2026Article
- The EAAT1 aspartate/glutamate transporter is dispensable for acute myeloid leukemia cell growth and response to therapy.PloS one · 2026Article
- Therapeutic targeting de novo purine biosynthesis driven by β-catenin-dependent PPAT upregulation in hepatoblastoma.Cell death & disease · 2025Article
- Introducing New Inhibitors of PAICS, aIranian journal of biotechnology · 2025Article
- Article
- Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells.Blood neoplasia · 2024Article
- Review
- Metabolic Profiling as an Approach to Differentiate T-Cell Acute Lymphoblastic Leukemia Cell Lines Belonging to the Same Genetic Subgroup.International journal of molecular sciences · 2024Article
- Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro.Biochemical pharmacology · 2024Article
- Silencing of Dicer enhances dacarbazine resistance in melanoma cells by inhibiting ADSL expression.Aging · 2023Article
- Applying CRISPR-Cas9 screens to dissect hematological malignancies.Blood advances · 2023Review
- CRISPR-Cas9 screen reveals a role of purine synthesis for estrogen receptor α activity and tamoxifen resistance of breast cancer cells.Science advances · 2023Article
- Targeting OXPHOS de novo purine synthesis as the nexus ofScience advances · 2022Article
- Reaction Mechanism of Human PAICS Elucidated by Quantum Chemical Calculations.Journal of the American Chemical Society · 2022Article
- Review
- Article
- Guanosine primes acute myeloid leukemia for differentiation via guanine nucleotide salvage synthesis.American journal of cancer research · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a devastating disease, and clinical outcomes are still far from satisfactory. Here, to identify novel targets for AML therapy, we performed a genome-wide CRISPR/Cas9 screen using AML cell lines, followed by a second screen in vivo. We show that PAICS, an enzyme involved in de novo purine biosynthesis, is a potential target for AML therapy. AML cells expressing shRNA-PAICS exhibited a proliferative disadvantage, indicating a toxic effect of shRNA-PAICS. Treatment of human AML cells with a PAICS inhibitor suppressed their proliferation by inhibiting DNA synthesis and promoting apoptosis and had anti-leukemic effects in AML PDX models. Furthermore, CRISPR/Cas9 screens using AML cells in the presence of the inhibitor revealed genes mediating resistance or synthetic lethal to PAICS inhibition. Our findings identify PAICS as a novel therapeutic target for AML and further define components of de novo purine synthesis pathway and its downstream effectors essential for AML cell survival.
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Registered trials
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.