ArticleCancer research2016
Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation.Molecular cancer research : MCR · 2024Article
- Sézary syndrome originates from heavily mutated hematopoietic progenitors.Blood advances · 2023Article
- Review
- Activity of the nonreceptor tyrosine kinase Ack1 is regulated by tyrosine phosphorylation of its Mig6 homology region.FEBS letters · 2022Article
- Chemical Reactivity and Optical and Pharmacokinetics Studies of 14 Multikinase Inhibitors and Their Docking Interactions Toward ACK1 for Precision Oncology.Frontiers in chemistry · 2022Article
- TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth.Nature communications · 2021Article
- Proximity-Dependent Biotinylation to Elucidate the Interactome of TNK2 Nonreceptor Tyrosine Kinase.Journal of proteome research · 2021Article
- Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6Journal of medicinal chemistry · 2020Article
- Research Progress of the Functional Role of ACK1 in Breast Cancer.BioMed research international · 2019Review
- Synthetic lethality of TNK2 inhibition in PTPN11-mutant leukemia.Science signaling · 2018Article
- Genome-Wide Identification and Characterization of Tyrosine Kinases in the Silkworm, Bombyx mori.International journal of molecular sciences · 2018Article
- Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.Molecular cancer · 2018Review
- Drug-perturbation-based stratification of blood cancer.The Journal of clinical investigation · 2018Article
- Crosstalk between VEGFR and other receptor tyrosine kinases for TKI therapy of metastatic renal cell carcinoma.Cancer cell international · 2018Review
- Identification and characterization of tyrosine kinases in anole lizard indicate the conserved tyrosine kinase repertoire in vertebrates.Molecular genetics and genomics : MGG · 2017Article
- Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade.Genes & development · 2017Article
- Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Histone deacetylase inhibitors induce proteolysis of activated CDC42-associated kinase-1 in leukemic cells.Journal of cancer research and clinical oncology · 2016Article
- Effect of protease inhibitors on the intraerythrocytic development of Babesia microti and Babesia duncani, the causative agents of human babesiosis.The Journal of eukaryotic microbiologyArticle
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
The amount of genomic information about leukemia cells currently far exceeds our overall understanding of the precise genetic events that ultimately drive disease development and progression. Effective implementation of personalized medicine will require tools to distinguish actionable genetic alterations within the complex genetic landscape of leukemia. In this study, we performed kinase inhibitor screens to predict functional gene targets in primary specimens from patients with acute myeloid leukemia and chronic myelomonocytic leukemia. Deep sequencing of the same patient specimens identified genetic alterations that were then integrated with the functionally important targets using the HitWalker algorithm to prioritize the mutant genes that most likely explain the observed drug sensitivity patterns. Through this process, we identified tyrosine kinase nonreceptor 2 (TNK2) point mutations that exhibited oncogenic capacity. Importantly, the integration of functional and genomic data using HitWalker allowed for prioritization of rare oncogenic mutations that may have been missed through genomic analysis alone. These mutations were sensitive to the multikinase inhibitor dasatinib, which antagonizes TNK2 kinase activity, as well as novel TNK2 inhibitors, XMD8-87 and XMD16-5, with greater target specificity. We also identified activating truncation mutations in other tumor types that were sensitive to XMD8-87 and XMD16-5, exemplifying the potential utility of these compounds across tumor types dependent on TNK2. Collectively, our findings highlight a more sensitive approach for identifying actionable genomic lesions that may be infrequently mutated or overlooked and provide a new method for the prioritization of candidate genetic mutations.
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