ArticleNature communications2023
Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06233526 (Individualized Treatment of Pediatric Relasped and Refractory Acute Myeloid Leukemia Based on Transcriptomic Profile and in Vitro Drug Sensitivity Test), which is not on this map. Cited by 14 papers.
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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.
Individualized Treatment of Pediatric Relasped and Refractory Acute Myeloid Leukemia Based on Transcriptomic Profile and in Vitro Drug Sensitivity Test
Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Bortezomib and vorinostat in combination with mitoxantrone, dexamethasone, and pegasparaginase during induction and reinduction for infants with acute lymphoblastic leukaemia: a multicentre single-arm phase 1/2 study.The Lancet. Haematology · 2026Trial
- Review
- Effect of the Proteasome Inhibitor, Bortezomib, on Histone Modifications in Human Leukemic Cell Lines.International journal of molecular sciences · 2026Article
- Review
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia.Scientific reports · 2025Article
- Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer.Scientific reports · 2025Article
- Preclinical Assessment of Dactinomycin inCancers · 2025Article
- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
- A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia.Leukemia · 2024Article
- Review
- Ruxolitinib inhibits the proliferation and induces the apoptosis of MLL-r ALL cells through inactivating JAK/STAT signaling pathway.Translational pediatrics · 2023Article
- Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2023Review
- The anti-leukemia activity and mechanisms of shikonin: a mini review.Frontiers in pharmacology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
33 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rearrangments in Histone-lysine-N-methyltransferase 2A (KMT2Ar) are associated with pediatric, adult and therapy-induced acute leukemias. Infants with KMT2Ar acute lymphoblastic leukemia (ALL) have a poor prognosis with an event-free-survival of 38%. Herein we evaluate 1116 FDA approved compounds in primary KMT2Ar infant ALL specimens and identify a sensitivity to proteasome inhibition. Upon exposure to this class of agents, cells demonstrate a depletion of histone H2B monoubiquitination (H2Bub1) and histone H3 lysine 79 dimethylation (H3K79me2) at KMT2A target genes in addition to a downregulation of the KMT2A gene expression signature, providing evidence that it targets the KMT2A transcriptional complex and alters the epigenome. A cohort of relapsed/refractory KMT2Ar patients treated with this approach on a compassionate basis had an overall response rate of 90%. In conclusion, we report on a high throughput drug screen in primary pediatric leukemia specimens whose results translate into clinically meaningful responses. This innovative treatment approach is now being evaluated in a multi-institutional upfront trial for infants with newly diagnosed ALL.
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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.