ArticleBlood advances2021
G9a/GLP targeting in MM promotes autophagy-associated apoptosis and boosts proteasome inhibitor-mediated cell death.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Inhibition of SUV39H1 as a potent therapeutic target in multiple myeloma.Haematologica · 2026Article
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Comparative Preclinical Evaluation of BIX-01294 and UNC0642 as EHMT2-Targeting Anticancer Agents.Cancers · 2026Article
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Inhibition of Histone Methyltransferase G9a Activates Autophagy and Provides Protection in Dry Eye Disease.Investigative ophthalmology & visual science · 2025Article
- Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma.Blood advances · 2025Article
- The de novo DNA methyltransferase 3B is a novel epigenetic regulator of MYC in multiple myeloma, representing a promising therapeutic target to counter relapse.Journal of experimental & clinical cancer research : CR · 2025Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- GLP and G9a histone methyltransferases as potential therapeutic targets for lymphoid neoplasms.Cancer cell international · 2024Review
- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- Epigenetic Regulation of Autophagy in Bone Metabolism.Function (Oxford, England) · 2024Review
- The Role and Mechanism of the Histone Methyltransferase G9a in Tumors: Update.OncoTargets and therapy · 2024Review
- Depletion of G9A attenuates imiquimod-induced psoriatic dermatitis via targeting EDAR-NF-κB signaling in keratinocyte.Cell death & disease · 2023Article
- High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach.Cancers · 2023Article
- Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma.Experimental hematology & oncology · 2023Article
- Article
- Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.Epigenetics & chromatin · 2022Article
- Identification of an Epi-metabolic dependency on EHMT2/G9a in T-cell acute lymphoblastic leukemia.Cell death & disease · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is an (epi)genetic highly heterogeneous plasma cell malignancy that remains mostly incurable. Deregulated expression and/or genetic defects in epigenetic-modifying enzymes contribute to high-risk disease and MM progression. Overexpression of the histone methyltransferase G9a was reported in several cancers, including MM, correlating with disease progression, metastasis, and poor prognosis. However, the exact role of G9a and its interaction partner G9a-like protein (GLP) in MM biology and the underlying mechanisms of action remain poorly understood. Here, we report that high G9a RNA levels are associated with a worse disease outcome in newly diagnosed and relapsed MM patients. G9a/GLP targeting using the specific G9a/GLP inhibitors BIX01294 and UNC0638 induces a G1-phase arrest and apoptosis in MM cell lines and reduces primary MM cell viability. Mechanistic studies revealed that G9a/GLP targeting promotes autophagy-associated apoptosis by inactivating the mTOR/4EBP1 pathway and reducing c-MYC levels. Moreover, genes deregulated by G9a/GLP targeting are associated with repressive histone marks. G9a/GLP targeting sensitizes MM cells to the proteasome inhibitors (PIs) bortezomib and carfilzomib, by (further) reducing mTOR signaling and c-MYC levels and activating p-38 and SAPK/JNK signaling. Therapeutic treatment of 5TGM1 mice with BIX01294 delayed in vivo MM tumor growth, and cotreatment with bortezomib resulted in a further reduction in tumor burden and a significantly prolonged survival. In conclusion, we provide evidence that the histone methyltransferases G9a/GLP support MM cell growth and survival by blocking basal autophagy and sustaining high c-MYC levels. G9a/GLP targeting represents a promising strategy to improve PI-based treatment in patients with high G9a/GLP levels.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.