ArticleBlood2019
Cirmtuzumab blocks Wnt5a/ROR1 stimulation of NF-κB to repress autocrine STAT3 activation in chronic lymphocytic leukemia.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Quantum Reactivity-Guided Optimization of ATP-Competitive Ligands through Multiscale Simulation.ACS physical chemistry Au · 2026Article
- Preclinical evaluation of the ROR1-targeting antibody-drug conjugates zilovertamab vedotin and VLS-211 against B-cell ALL patient-derived xenografts.HemaSphere · 2026Article
- Focal adhesion kinase FAK interplays with ROR1 in the aggressiveness of chronic lymphocytic leukemia.BMC medicine · 2026Article
- Wnt5a suppresses colorectal cancer progression via TGF-β/NOTUM/OLFM4 axis in patient-derived organoids.Cell communication and signaling : CCS · 2025Article
- Wnt5a induces ROR1 dependent NF-κB activation to enhance MMP-9 expression and invasiveness in chronic lymphocytic leukemia.Leukemia · 2025Article
- Unlocking the potential: advancements and future horizons in ROR1-targeted cancer therapies.Science China. Life sciences · 2024Review
- Therapeutic advances in the targeting of ROR1 in hematological cancers.Cell death discovery · 2024Review
- Transcriptomic and proteomic differences in BTK-WT and BTK-mutated CLL and their changes during therapy with pirtobrutinib.Blood advances · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Inflammation mediated angiogenesis in chronic lymphocytic leukemia.Annals of hematology · 2024Article
- Variant Transcript of ROR1 ENST00000545203 Does Not Encode ROR1 Protein.Biomedicines · 2024Article
- Receptor tyrosine kinase-like orphan receptor 1: A novel antitumor target in gastrointestinal cancers.World journal of clinical oncology · 2024Review
- Article
- Non-canonical transcriptional regulation of the poor prognostic factor UGT2B17 in chronic lymphocytic leukemic and normal B cells.BMC cancer · 2024Article
- miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.Cell death discovery · 2023Article
- ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity.Cell death discovery · 2023Article
- Association of baseline ROR1 and ROR2 gene expression with clinical outcomes in the I-SPY2 neoadjuvant breast cancer trial.Breast cancer research and treatment · 2023Article
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- To β or Not to β: How Important Is β-Catenin Dependent and Independent WNT Signaling in CLL?Cancers · 2022Review
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Coculture of nurse-like cells (NLCs) with chronic lymphocytic leukemia (CLL) cells induced leukemia cell phosphorylation of STAT3 (pSTAT3), which could be blocked by anti-Wnt5a antibodies or the anti-ROR1 monoclonal antibody, cirmtuzumab. Time-course studies revealed Wnt5a could induce activation of NF-κB within 30 minutes, but required more than 3 hours to induce pSTAT3. Culture of isolated CLL cells for 24 hours revealed Wnt5a-induced expression of interleukin 6 (IL-6), IL-8, CCL2, CCL3, CCL4, and CXCL1, which in turn could induce pSTAT3 in unstimulated CLL cells within 30 minutes. We found that Wnt5a could induce CLL cell expression of NF-κB target genes, including IL-6, and that this effect could be blocked by cirmtuzumab or drugs that inhibit NF-κB. Examination of CLL cells and plasma collected from patients treated with cirmtuzumab revealed reduced levels of phosphorylated p65 and diminished expression of NF-κB and STAT3 target genes in CLL cells, as well as lower plasma levels of IL-6, in the samples after therapy. Collectively, these studies indicate that Wnt5a/ROR1-dependent signaling contributes to CLL cell activation of NF-κB, which in turn causes autocrine IL-6-induced activation of pSTAT3. As such, this study demonstrates that cirmtuzumab can inhibit leukemia cell activation of both NF-κB and STAT3 in patients with CLL.
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