ArticleNPJ precision oncology2021
Acquired JAK2 mutations confer resistance to JAK inhibitors in cell models of acute lymphoblastic leukemia.
Article in NPJ precision oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Large-scale comparative virtual screening identifies novel molecular targets underlying the multi-target activity of quercetin in psoriasis.Inflammopharmacology · 2026Article
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- The Mechanisms of Resistance to JAK Inhibitors in Lymphoid Leukemias: A Scoping Review of Evidence from Preclinical Models and Case Reports.International journal of molecular sciences · 2025Article
- Mucosal implications of oral Jak3-targeted drugs in COVID patients.Molecular medicine (Cambridge, Mass.) · 2025Review
- Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.Cancer immunology, immunotherapy : CII · 2025Article
- Direct STAT3 and STAT5 Inhibition Overcomes Treatment Resistance in a Murine-Derived in vitro Model of Acute Lymphoblastic Leukaemia Driven by <italic>ETV6::JAK2</italic>.Acta haematologica · 2025Article
- The Role of the JAK-STAT Pathway in Childhood B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Review
- Type II mode of JAK2 inhibition and destabilization are potential therapeutic approaches against the ruxolitinib resistance driven myeloproliferative neoplasms.Frontiers in oncology · 2024Article
- Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.iScience · 2023Article
- New scaffolds for type II JAK2 inhibitors overcome the acquired G993A resistance mutation.Cell chemical biology · 2023Article
- Resistance Mechanisms in Pediatric B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Review
- Understanding Aberrant Signaling to Elude Therapy Escape Mechanisms in Myeloproliferative Neoplasms.Cancers · 2022Review
- Molecular dissection of Janus kinases as drug targets for inflammatory diseases.Frontiers in immunology · 2022Review
- Review
- Acquired JAK2 mutations confer resistance to JAK inhibitors in cell models of acute lymphoblastic leukemia.NPJ precision oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Ruxolitinib (rux) Phase II clinical trials are underway for the treatment of high-risk JAK2-rearranged (JAK2r) B-cell acute lymphoblastic leukemia (B-ALL). Treatment resistance to targeted inhibitors in other settings is common; elucidating potential mechanisms of rux resistance in JAK2r B-ALL will enable development of therapeutic strategies to overcome or avert resistance. We generated a murine pro-B cell model of ATF7IP-JAK2 with acquired resistance to multiple type-I JAK inhibitors. Resistance was associated with mutations within the JAK2 ATP/rux binding site, including a JAK2 p.G993A mutation. Using in vitro models of JAK2r B-ALL, JAK2 p.G993A conferred resistance to six type-I JAK inhibitors and the type-II JAK inhibitor, CHZ-868. Using computational modeling, we postulate that JAK2 p.G993A enabled JAK2 activation in the presence of drug binding through a unique resistance mechanism that modulates the mobility of the conserved JAK2 activation loop. This study highlights the importance of monitoring mutation emergence and may inform future drug design and the development of therapeutic strategies for this high-risk patient cohort.
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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.