ArticleThe Journal of clinical investigation2020
Oncogene-independent BCR-like signaling adaptation confers drug resistance in Ph-like ALL.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A meta-analysis of diagnostic challenges in Ph-like ALL at baseline: early detection strategies for personalized therapeutic interventions.International journal of hematology · 2025Pooled it
- Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium.Cancer discovery · 2021Trial
- β3-adrenergic blockade targets fatty acid oxidation to induce ferroptotic vulnerability in pediatric T-ALL.Biology direct · 2026Article
- 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
- An antibody-drug conjugate targeting VpreB1 for the treatment of B-cell acute lymphoblastic leukemia.Blood neoplasia · 2025Article
- Targeting Artemis Sensitizes B Cells to Topoisomerase 2 Poisons by Disrupting DNA-PKcs-Dependent Repair.Research square · 2025Article
- Memory-like Natural Killer Cell and CD19 Antibody-Based Immunotherapy in Combination with Tyrosine Kinase Inhibition Has Antitumor Effects against Ph(-like) Acute Lymphoblastic Leukemia.Cancer immunology research · 2025Article
- The Struggle Between Chimeric Antigen Receptor T-Cell Therapy and Neurological Complications in Acute Lymphoblastic Leukemia Treatment.Current issues in molecular biology · 2025Review
- Bridging the Gap: Cost-Effective Strategies for Detecting Ph-Like B-Lineage ALL in Resource-Limited Settings.Molecular diagnosis & therapy · 2025Review
- DYRK1A inhibition results in MYC and ERK activation rendering KMT2A-R acute lymphoblastic leukemia cells sensitive to BCL2 inhibition.Leukemia · 2025Article
- Targeting senescent stemlike subpopulations in Philadelphia chromosome-like acute lymphoblastic leukemia.Blood · 2025Article
- Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia.Cancer cell · 2025Article
- Article
- Review
- Thymic stromal lymphopoietin in leukemia: A double-edged sword?Leukemia research reports · 2025Review
- 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
- Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities.Nature communications · 2024Article
- Mutation and cell state compatibility is required and targetable in Ph+ acute lymphoblastic leukemia minimal residual disease.bioRxiv : the preprint server for biology · 2024Article
- Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells.Blood neoplasia · 2024Article
- Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Children and adults with Philadelphia chromosome-like B cell acute lymphoblastic leukemia (Ph-like B-ALL) experience high relapse rates despite best-available conventional chemotherapy. Ph-like ALL is driven by genetic alterations that activate constitutive cytokine receptor and kinase signaling, and early-phase trials are investigating the potential of the addition of tyrosine kinase inhibitors (TKIs) to chemotherapy to improve clinical outcomes. However, preclinical studies have shown that JAK or PI3K pathway inhibition is insufficient to eradicate the most common cytokine receptor-like factor 2-rearranged (CRLF2-rearranged) Ph-like ALL subset. We thus sought to define additional essential signaling pathways required in Ph-like leukemogenesis for improved therapeutic targeting. Herein, we describe an adaptive signaling plasticity of CRLF2-rearranged Ph-like ALL following selective TKI pressure, which occurs in the absence of genetic mutations. Interestingly, we observed that Ph-like ALL cells have activated SRC, ERK, and PI3K signaling consistent with activated B cell receptor (BCR) signaling, although they do not express cell surface μ-heavy chain (μHC). Combinatorial targeting of JAK/STAT, PI3K, and "BCR-like" signaling with multiple TKIs and/or dexamethasone prevented this signaling plasticity and induced complete cell death, demonstrating a more optimal and clinically pragmatic therapeutic strategy for CRLF2-rearranged Ph-like ALL.
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