ArticleBlood2020
The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 82 citations in OpenAlex.
- Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial.Signal transduction and targeted therapy · 2024Trial
- Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma.Blood advances · 2021Trial
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- Selection of anti-CD38 antibodies for flow cytometric detection of myeloma cells treated with daratumumab or isatuximab.International journal of hematology · 2026Article
- Emerging chemical strategies for CD38 inhibition: restoring NADBioorganic & medicinal chemistry · 2026Review
- Differential regulation of monocyte exhaustion by distinct TLR agonists and underlying mechanisms.Cell communication and signaling : CCS · 2026Article
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Monocyte-mediated metabolic rewiring via CD31-CD38 interactions promotes growth and drug-resistance in multiple myeloma.HemaSphere · 2026Article
- Ly93 Inhibits Sphingomyelin Synthesis and Attenuates Inflammation and Injury in Dry Eye Conjunctival Organoids.Investigative ophthalmology & visual science · 2026Article
- Selinexor potentiates NK cell activation against multiple myeloma.Clinical and experimental immunology · 2026Article
- Modulating CD38 enzymatic activity during antibody-based immunotherapy in multiple myeloma: a basic science perspective.Frontiers in immunology · 2026Article
- Targeting Wnt/β-catenin signaling enhances the efficacy of anti-CD38 immunotherapy in multiple myeloma.Neoplasia (New York, N.Y.) · 2025Article
- Reduced ALDH1A1 expression in multiple myeloma cells increases resistance to daratumumab via downregulation of retinoic acid.Cellular and molecular life sciences : CMLS · 2025Article
- Breaking Barriers: The Role of the Bone Marrow Microenvironment in Multiple Myeloma Progression.International journal of molecular sciences · 2025Review
- Multiple myeloma with 1q gain/amplification exhibits reduced CD38 expression via interleukin-6 receptor overexpression.British journal of haematology · 2025Article
- Overview of 1q abnormalities in multiple myeloma: scientific opinions from Italian experts.Annals of hematology · 2025Review
- Leveraging a disulfidptosis-based signature to characterize heterogeneity and optimize treatment in multiple myeloma.Frontiers in immunology · 2025Article
- Deciphering the bone marrow microenvironment's role in multiple myeloma immunotherapy resistance.Frontiers in immunology · 2025Review
- Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects.Frontiers in immunology · 2025Review
- Functional multiomics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma.Blood neoplasia · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Anti-CD38 monoclonal antibody (MoAb) treatments including daratumumab (DARA) are effective therapies for both newly diagnosed and relapsed multiple myeloma (MM). In this study, we examined the soluble factors that modulate CD38 expression and are associated with sensitivity to DARA-mediated antibody-dependent cellular cytotoxicity (ADCC) in the bone marrow (BM) microenvironment. Importantly, primary BM stromal cell (BMSC) culture supernatant (BMSC-sup) and interleukin-6 (IL-6) downregulated CD38 expression and reduced DARA-mediated ADCC. Both cytokine profiling of the BMSC-sup and genome-scale clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) knockout screening in MM cell lines identified and validated the JAK-STAT3 signaling pathway mediating CD38 downregulation, whereas the JAK-STAT1 pathway mediated CD38 upregulation. STAT3 knockdown abrogated BMSC-sup- and IL-6-induced CD38 downregulation on MM cell lines. We also confirmed that STAT3 and CD38 is negatively correlated in primary MM cells. To assess potential clinical relevance, pharmacological inhibition of the JAK-STAT pathway on BMSC-sup-induced CD38 downregulation was further examined. JAK inhibitor ruxolitinib inhibited STAT3 phosphorylation in MM cell lines, upregulated CD38 expression in MM cell lines and primary patient MM cells, and augmented DARA-mediated ADCC against MM cell lines. Taken together, our results suggest that CD38 expression on MM cells in the BM microenvironment is regulated by both STAT1 (positively) and STAT3 (negatively), and that inhibition of the JAK-STAT3 pathway represents a novel therapeutic option to enhance CD38 expression and anti-CD38 MoAb-mediated MM cytotoxicity.
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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.