ArticleOncogene2015
A targeted knockdown screen of genes coding for phosphoinositide modulators identifies PIP4K2A as required for acute myeloid leukemia cell proliferation and survival.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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Who cites it
55 citing papers in PubMed, 83 citations in OpenAlex.
- PIP4K2A depletion suppresses AKT signaling and enhances chemotherapy sensitivity in T-cell lymphoblastic lymphoma cells.Biochemical and biophysical research communications · 2026Article
- PIP4K2A Attenuates Cerebral Ischemia/Reperfusion Injury by Reducing the TRIB3-p62 Complex Burden and Modulating AKT/mTOR Signaling.Translational stroke research · 2026Article
- Article
- PI5P4K inhibitors: promising opportunities and challenges.The FEBS journal · 2025Review
- Downregulation of PIP4K2C inhibits the breast cancer cell proliferation, migration and invasion.Translational oncology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Expression quantitative trait loci influence DNA damage-induced apoptosis in cancer.BMC genomics · 2024Article
- Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms.Journal of translational medicine · 2024Article
- Prognostic prediction using a gene signature developed based on exhausted T cells for liver cancer patients.Heliyon · 2024Article
- PIP4K2B Protein Regulation by NSD1 in HPV-Negative Head and Neck Squamous Cell Carcinoma.Cancers · 2024Article
- Metabolic Enzyme SLC27A5 Regulates PIP4K2A pre-mRNA Splicing as a Noncanonical Mechanism to Suppress Hepatocellular Carcinoma Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Pharmacological Inhibition of PIP4K2 Potentiates Venetoclax-Induced Apoptosis in Acute Myeloid Leukemia.International journal of molecular sciences · 2023Article
- The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K).RSC medicinal chemistry · 2023Article
- Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci.Precision clinical medicine · 2023Article
- Identification of ARUK2002821 as an isoform-selective PI5P4Kα inhibitor.RSC medicinal chemistry · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Targeting the Dark Lipid Kinase PIP4K2C with a Potent and Selective Binder and Degrader.Angewandte Chemie (International ed. in English) · 2023Article
- Development of potent and selective degraders of PI5P4Kγ.European journal of medicinal chemistry · 2023Article
- PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition.Science advances · 2023Article
- Modelling PIP4K2A inhibitory activity of 1,7-naphthyridine analogues using machine learning and molecular docking studies.RSC advances · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Given the importance of deregulated phosphoinositide (PI) signaling in leukemic hematopoiesis, genes coding for proteins that regulate PI metabolism may have significant and as yet unappreciated roles in leukemia. We performed a targeted knockdown (KD) screen of PI modulator genes in human acute myeloid leukemia (AML) cells and identified candidates required to sustain proliferation or prevent apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A) regulates cellular levels of phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂). We found PIP4K2A to be essential for the clonogenic and leukemia-initiating potential of human AML cells, and for the clonogenic potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for the clonogenic potential of primary human AML cells. Its KD results in accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G₁ cell cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially dependent on activation of the mTOR pathway. Critically, however, PIP4K2A KD in normal hematopoietic stem and progenitor cells, both murine and human, did not adversely impact either clonogenic or multilineage differentiation potential, indicating a selective dependency that we suggest may be the consequence of the regulation of different transcriptional programs in normal versus malignant cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid malignancy.
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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.