ArticleThe Journal of clinical investigation2016
Hedgehog and retinoid signaling alters multiple myeloma microenvironment and generates bortezomib resistance.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06109233 (A Perspective Study of the MRD-tailored Therapy in Patients With Newly Diagnosed Multiple Myeloma With Persistent Minimal Residual Disease After Initial Treatment), which is not on this map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Perspective Study of the MRD-tailored Therapy in Patients With Newly Diagnosed Multiple Myeloma With Persistent Minimal Residual Disease After Initial Treatment
Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results.American journal of hematology · 2018Trial
- Overcoming resistance in CD44-overexpressing myeloma through combination therapy with ATRA, bortezomib, and NK cells.Cancer immunology, immunotherapy : CII · 2026Article
- [The role and molecular mechanism of transcription factor EB and its target genes in multiple myeloma treatment with bortezomib].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Review
- Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells.Heliyon · 2024Review
- Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy.MedComm · 2023Review
- Article
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- Review
- Review
- The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.Frontiers in cell and developmental biology · 2021Review
- Article
- Transcription Factors in Cancer Development and Therapy.Cancers · 2020Review
- CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF-MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement.The oncologist · 2020Article
- Targeting the Microenvironment in MDS: The Final Frontier.Frontiers in pharmacology · 2020Review
- A Phase 1 Study of IRX195183, a RARα-Selective CYP26 Resistant Retinoid, in Patients With Relapsed or Refractory AML.Frontiers in oncology · 2020Article
- Novel p97/VCP inhibitor induces endoplasmic reticulum stress and apoptosis in both bortezomib-sensitive and -resistant multiple myeloma cells.Cancer science · 2019Article
- Regulation of drug metabolizing enzymes in the leukaemic bone marrow microenvironment.Journal of cellular and molecular medicine · 2019Article
- Sonic Hedgehog Signaling Is Required for Cyp26 Expression during Embryonic Development.International journal of molecular sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in bortezomib (BTZ) resistance. However, the mechanisms involved in these interactions are not completely understood. We previously showed that expression of CYP26 in BM stromal cells maintains a retinoic acid-low (RA-low) microenvironment that prevents the differentiation of normal and malignant hematopoietic cells. Since a low secretory B cell phenotype is associated with BTZ resistance in MM and retinoid signaling promotes plasma cell differentiation and Ig production, we investigated whether stromal expression of the cytochrome P450 monooxygenase CYP26 modulates BTZ sensitivity in the BM niche. CYP26-mediated inactivation of RA within the BM microenvironment prevented plasma cell differentiation and promoted a B cell-like, BTZ-resistant phenotype in human MM cells that were cocultured on BM stroma. Moreover, paracrine Hedgehog secretion by MM cells upregulated stromal CYP26 and further reinforced a protective microenvironment. These results suggest that crosstalk between Hedgehog and retinoid signaling modulates BTZ sensitivity in the BM niche. Targeting these pathological interactions holds promise for eliminating minimal residual disease in MM.
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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.