ArticleNature chemical biology2012
BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 183 citations in OpenAlex.
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- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- BCR::ABL1 Proteolysis-targeting chimeras (PROTACs): The new frontier in the treatment of PhLeukemia · 2024Review
- CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.Journal of cellular and molecular medicine · 2024Article
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
- C/EBPβ-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor biology.Stem cell reports · 2024Article
- A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo.Nature chemical biology · 2023Article
- Induction of DNMT1-dependent demethylation of SHP-1 by the natural flavonoid compound Baicalein overcame Imatinib-resistance in CML CD34Cell communication and signaling : CCS · 2023Article
- Recent advancements in targeted protein knockdown technologies-emerging paradigms for targeted therapy.Exploration of targeted anti-tumor therapy · 2023Review
- PROTACs: Walking through hematological malignancies.Frontiers in pharmacology · 2023Review
- Recent Advances in PROTACs for Drug Targeted Protein Research.International journal of molecular sciences · 2022Review
- circCRKL, a circRNA derived from CRKL, regulates BCR-ABL via sponging miR-877-5p to promote chronic myeloid leukemia cell proliferation.Journal of translational medicine · 2022Article
- SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia.Blood advances · 2022Article
- Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance.Leukemia · 2021Article
- Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets.Leukemia · 2021Article
- TRAM-Related TLR4 Pathway Antagonized by IRAK-M Mediates the Expression of Adhesion/Coactivating Molecules on Low-Grade Inflammatory Monocytes.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells.Archives of medical science : AMS · 2021Article
- Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells.Frontiers in oncology · 2021Review
38 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutive activation of STAT5 is critical for the maintenance of chronic myeloid leukemia (CML) characterized by the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (TKIs) for the STAT5-activating kinase JAK2 have been discussed as a treatment option for CML patients. Using murine leukemia models combined with inducible ablation of JAK2, we show JAK2 dependence for initial lymphoid transformation, which is lost once leukemia is established. In contrast, initial myeloid transformation and leukemia maintenance were independent of JAK2. Nevertheless, several JAK2 TKIs induced apoptosis in BCR-ABL(+) cells irrespective of the presence of JAK2. This is caused by the previously unknown direct 'off-target' inhibition of BCR-ABL. Cellular and enzymatic analyses suggest that BCR-ABL phosphorylates STAT5 directly. Our findings suggest uncoupling of the canonical JAK2-STAT5 module upon BCR-ABL expression, thereby making JAK2 targeting dispensable. Thus, attempts to pharmacologically target STAT5 in BCR-ABL(+) diseases need to focus on STAT5 itself.
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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.