Affinage

Showing KMT2A — MLL1 is a alias.

KMT2A

Histone-lysine N-methyltransferase 2A · UniProt Q03164

Length
3969 aa
Mass
431.8 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KMT2A (MLL1/HRX/ALL-1) is a nuclear histone H3K4 methyltransferase that binds DNA and deposits activating H3K4me3 to control developmental and signal-responsive gene programs (PMID:9158002, PMID:36635503). It engages chromatin through its own DNA-binding modules: recombinant AT-hook subdomains bind double-stranded DNA non-sequence-specifically while a zinc-binding (CXXC) subdomain supports sequence-specific binding, and a CXXC-domain missense variant disturbs KMT2A subcellular distribution and target-gene expression in patient cells (PMID:9158002, PMID:29203834). A menin-dependent KMT2A complex occupies active gene promoters; loss of the menin interaction redistributes KMT2A to bivalent promoters, revealing a menin-independent function in maintaining H3K4me3 and opposing polycomb-mediated repression, and loss of KMT2C/D similarly redirects the KMT2A-menin complex from enhancers to CpG-high and bivalent promoters (PMID:36635503, PMID:39806204). KMT2A is recruited to specific targets by partner factors — NF-κB/RelA (p65) brings it to the CTSZ promoter to drive colorectal invasion and to procoagulant/proinflammatory loci in monocytes/macrophages, while an enhancer-derived lncRNA (Myrlin) recruits the KMT2A complex to the Myb locus to license productive RNA Pol II elongation (PMID:31090199, PMID:36493338, PMID:38889007). Through these target programs KMT2A activates transcription of genes including hTERT in melanoma and METTL3 in nucleus pulposus cells, and in hippocampal neurons it deposits locus-specific H3K4 methylation required for memory, acting in mutual antagonism with the demethylase KDM5C (PMID:28726783, PMID:39572532, PMID:28723559, PMID:32483278). In leukemia, chromosomal translocations fuse the N-terminal AT-hook/DNA-binding region of KMT2A to partner proteins (ENL, AF-4/FEL, AF-9, AF-10, ELL) that donate transcriptional activation domains, converting it into a gain-of-function oncogenic transcription factor; the ENL C-terminal ~84–90 residues are necessary and sufficient for both transactivation and transformation, and AT-hook DNA binding plus the methyltransferase-homology domain are required for the oncogenic activity (PMID:9250666, PMID:9418860, PMID:8080983, PMID:9403001). The menin–KMT2A protein–protein interaction is the functional oncogenic dependency: small-molecule inhibitors (revumenib, bleximenib) displace the complex from target promoters such as MEIS1 and FLT3, downregulate the KMT2A signature, and induce leukemic differentiation and clinical remission (PMID:36922593, PMID:39121437, PMID:38905635).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 Medium

    Established the molecular architecture of the leukemic fusions, showing that translocation partners (FEL/AF-4, ENL) are joined in-frame to the N-terminal AT-hook-containing portion of KMT2A and that the partners carry intrinsic transcriptional activation domains.

    Evidence cDNA cloning and sequencing of t(4;11) fusion transcripts; deletion mutagenesis and transcriptional reporter assays for ENL across lymphoid, myeloid, and yeast systems

    PMID:8080983 PMID:8443374

    Open questions at the time
    • No functional reconstitution of the FEL fusion's transforming activity in these studies
    • Mechanism by which the partner activation domain reprograms KMT2A targets not defined
  2. 1996 Medium

    Identified early physical partners of the KMT2A N-terminus (UNR, with cold-shock domains), beginning the mapping of its protein interaction network.

    Evidence Yeast two-hybrid screen, in vitro binding, and co-IP from COS cells

    PMID:8934551

    Open questions at the time
    • Functional consequence of the UNR interaction not established
    • Single-lab interaction without in vivo validation
  3. 1997 Medium

    Defined how KMT2A engages chromatin and assembles regulatory heterocomplexes, showing AT-hook and zinc-binding DNA-binding modes, nuclear punctate localization, and direct association with the SET–PP2A complex.

    Evidence Recombinant subdomain DNA-binding assays, immunolocalization, yeast two-hybrid, co-IP, and site-directed mutagenesis with phosphatase activity readout

    PMID:9041173 PMID:9129043 PMID:9158002 PMID:9353299 PMID:9403001

    Open questions at the time
    • Sequence-specific DNA targets in vivo not identified
    • Role of the SET–PP2A heterocomplex in normal KMT2A function unresolved
  4. 1998 High

    Dissected the gain-of-function requirements of an MLL fusion, showing transformation requires KMT2A AT-hooks and methyltransferase-homology domain plus the partner's transactivation domain, directly linking transactivation to oncogenesis.

    Evidence Structure-function deletion analysis with in vitro myeloid immortalization, DNA-binding, and transactivation assays; in vivo leukemia induction by HRX-ENL

    PMID:9250666 PMID:9418860

    Open questions at the time
    • Did not identify the chromatin targets responsible for transformation
    • Mechanistic link between DNA binding and aberrant transcription not resolved at the gene level
  5. 1999 High

    Connected KMT2A and its fusions to apoptotic control, showing wild-type KMT2A enhances GADD34-induced apoptosis while fusions inhibit it.

    Evidence Yeast two-hybrid, reciprocal co-IP, and overexpression apoptosis assays after ionizing radiation with three fusion proteins versus wild-type

    PMID:10490642

    Open questions at the time
    • Physiological relevance of the GADD34 axis to leukemogenesis not demonstrated in vivo
    • Link to KMT2A's methyltransferase activity unexplored
  6. 2017 Medium

    Extended KMT2A function beyond leukemia, showing locus-specific H3K4 methylation roles in neuronal memory and oncogenic activation of hTERT in melanoma.

    Evidence Mouse Kmt2a knockdown with H3K4me ChIP and memory behavior; melanoma KMT2A knockdown/overexpression with hTERT promoter reporter and rescue

    PMID:28723559 PMID:28726783

    Open questions at the time
    • Recruitment mechanism to neuronal and hTERT loci not defined
    • Single-lab studies
  7. 2019 Medium

    Identified a recruitment logic for non-leukemic KMT2A targeting, showing NF-κB/p65 recruits KMT2A to the CTSZ promoter to drive metastasis.

    Evidence KMT2A knockdown in colorectal cells, xenograft metastasis model, and ChIP showing p65-dependent KMT2A occupancy

    PMID:31090199

    Open questions at the time
    • Direct p65–KMT2A physical interaction not biochemically resolved
    • Generality of p65-directed recruitment beyond CTSZ untested here
  8. 2020 Medium

    Defined a chromatin balance principle, showing KMT2A and the demethylase KDM5C act in mutual antagonism such that combined loss rescues single-mutant epigenomic and behavioral defects.

    Evidence Double-mutant mouse genetics with dendritic spine, behavioral, H3K4me ChIP-seq, and RNA-seq readouts

    PMID:32483278

    Open questions at the time
    • Whether antagonism is direct or via shared targets not resolved
    • Restricted to neuronal context
  9. 2023 High

    Established the menin–KMT2A interaction as the therapeutic oncogenic dependency and distinguished menin-dependent active-gene occupancy from a menin-independent bivalent-gene function.

    Evidence First-in-human revumenib trial with differentiation correlatives; genome-wide CRISPR screens and H3K4me3/H3K27me3 ChIP-seq with genetic and pharmacological menin perturbation

    PMID:36635503 PMID:36922593 PMID:39121437

    Open questions at the time
    • Molecular basis of menin-independent bivalent maintenance not fully defined
    • Determinants of redistribution between active and bivalent loci unresolved
  10. 2023 Medium

    Linked KMT2A to inflammatory/coagulation transcription and to histone-mark dependencies, placing it downstream of NF-κB/RelA in macrophages and within a proteasome-sensitive H2Bub1/H3K79me2 axis in KMT2A-rearranged ALL.

    Evidence Conditional MLL1 macrophage knockout in a coronavirus model with NF-κB reporters; drug screen in primary KMT2Ar infant ALL with H2Bub1/H3K79me2 ChIP and signature profiling

    PMID:36493338 PMID:36781850

    Open questions at the time
    • Direct KMT2A–RelA biochemical interaction not mapped
    • Mechanism linking proteasome activity to histone marks at KMT2A targets indirect
  11. 2024 Medium

    Resolved the structural basis and target consequences of menin–KMT2A inhibition and identified RNA-guided recruitment, showing bleximenib's distinct binding mode displaces the complex from MEIS1/FLT3 and that lncRNA Myrlin recruits KMT2A to license Myb elongation.

    Evidence Menin–inhibitor co-crystal structure with ChIP-seq and xenograft validation; RNA-IP, ChIP, and 3C at the Myb locus with CRISPRi

    PMID:38889007 PMID:38905635

    Open questions at the time
    • Generality of lncRNA-mediated recruitment across loci unknown
    • How KMT2A occupancy controls Pol II pause release mechanistically incomplete
  12. 2025 High

    Showed that KMT2A genomic positioning is dictated by sister methyltransferases, with KMT2C/D loss redistributing the KMT2A-menin complex from enhancers to bivalent/CpG-high promoters and derepressing immediate-early genes.

    Evidence Kmt2c/d knockout mouse models with KMT2A, H3K4me1, H3K27ac ChIP-seq and nascent transcription assays

    PMID:39806204

    Open questions at the time
    • Whether redistribution is competitive or signal-dependent not fully resolved
    • Consequences for human tumors beyond urothelium untested here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KMT2A's catalytic H3K4 methyltransferase activity is mechanistically coupled to its diverse recruitment routes (NF-κB, lncRNAs, menin, sister KMTs) and how this determines locus-specific outcomes remains unresolved.
  • No unified model of how recruitment factors select between active and bivalent targets
  • Direct in vivo structure of the assembled KMT2A complex on chromatin not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0016740 transferase activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-168256 Immune System 1
Partners
AFF1CSDE1ENLGADD34MEN1PP2ARELASET
Complex memberships
SET-PP2A heterocomplexmenin-KMT2A complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 HRX-ENL fusion protein immortalizes myelomonocytic precursors and induces myeloid leukemia in vivo; a deletion mutant of HRX-ENL lacking the ENL component failed to transform, demonstrating that the ENL portion is required for oncogenic gain-of-function. Retroviral gene transfer into hematopoietic stem cells, in vitro colony replating assays, transplantation into syngeneic and SCID mice The EMBO journal High 9250666
1998 Oncogenic activity of HRX-ENL requires: (1) the AT-hook motifs of HRX for DNA binding, (2) the methyltransferase homology domain of HRX (shown to bind DNA non-sequence-specifically in vitro), and (3) the C-terminal 84 amino acids of ENL which are necessary and sufficient for transcriptional activation and correlate with transforming activity. Structure-function deletion analysis, in vitro myeloid immortalization assay, in vitro DNA-binding assay, transcriptional transactivation assays Molecular and cellular biology High 9418860
1994 In t(4;11) leukemias, HRX is fused in-frame to FEL (AF-4), a serine/proline-rich protein; the fusion places 913 C-terminal amino acids of FEL onto the N-terminal portion of HRX containing its AT-hook DNA-binding motifs. cDNA cloning, Northern blot, sequence analysis of fusion transcripts Blood Medium 8443374
1994 ENL, the t(11;19) fusion partner of HRX, is a nuclear protein with intrinsic transcriptional activation activity in both lymphoid and myeloid cells; the minimal transactivation domain maps to the C-terminal 90 amino acids, which are also conserved in AF-9 and retained in all HRX-ENL fusion proteins. Deletion mutagenesis, transcriptional reporter assays in lymphoid cells, myeloid cells, and yeast Blood High 8080983
1999 HRX proteins interact directly with GADD34; three different HRX fusion proteins (HRX-ENL, HRX-AF9, HRX-ELL) inhibit GADD34-induced apoptosis after ionizing radiation, whereas wild-type HRX enhances apoptosis. GADD34 also binds hSNF5/INI1, a chromatin-remodeling complex subunit. Yeast two-hybrid, co-immunoprecipitation from human cells, overexpression apoptosis assays with ionizing radiation Molecular and cellular biology High 10490642
1997 A region of HRX consistently retained in leukemic fusion proteins interacts directly with SET (a leukemia-associated protein) near the AT-hook domains; a single amino acid mutation in the SET-binding site reduces both co-immunoprecipitated SET and co-immunoprecipitated protein phosphatase 2A (PP2A), indicating HRX forms a heterocomplex with SET and PP2A. Yeast two-hybrid, in vitro binding studies, co-immunoprecipitation, site-directed mutagenesis, phosphatase activity assay with okadaic acid The Journal of biological chemistry High 9353299
1997 Wild-type HRX/ALL-1 protein localizes to nuclear structures in a punctate distribution, whereas the HRX/ALL-1-eps15 fusion protein localizes exclusively to the nucleus in bodies that are smaller and more numerous, indicating fusion with eps15 alters the subcellular compartmentalization of HRX. Immunocytochemistry with polyclonal and monoclonal antibodies; Western blot of cells with 11q23 translocations; transfection with HRX-ENL fusion gene for antibody validation Blood / Cancer research Medium 9041173 9129043
1997 The FEL (AF-4) protein donates transcriptional activation sequences to HRX-FEL fusion proteins; the transactivating region maps to amino acids 365–572 of FEL, which is consistently retained in HRX-FEL fusions created by t(4;11) translocations. Gal4-fusion transcriptional reporter assays in multiple cell lines Leukemia research Medium 9403001
1996 The N-terminal segment of ALL-1 interacts with UNR, a protein containing multiple cold shock domains (CSD); the minimal region of UNR required includes two CSD and two intervening polypeptides. Interaction confirmed by in vitro binding and co-immunoprecipitation from COS cells. Yeast two-hybrid screening, in vitro binding studies, co-immunoprecipitation from COS cells Oncogene Medium 8934551
1997 The ALL-1 protein is predominantly localized in the nucleus; recombinant AT-hook and zinc-binding subdomains of ALL-1 interact in vitro with double-stranded oligodeoxynucleotides, supporting both sequence-unspecific (AT-hook) and sequence-specific (zinc-binding) DNA-binding modes. Anti-ALL-1 antisera immunolocalization, Western blot, in vitro DNA-binding assay with recombinant protein subdomains Cancer research Medium 9158002
2017 KMT2A (H3K4 methyltransferase) controls largely distinct genomic regions and molecular pathways from KMT2B in hippocampal neurons; Kmt2a knockdown decreases H3K4 methylation at specific loci and impairs memory formation in mice. Mouse knockdown model, H3K4 methylation ChIP analysis, gene expression profiling, behavioral memory tests Cell reports Medium 28723559
2020 KMT2A and the H3K4 demethylase KDM5C have mutually suppressive roles; double mutation of Kmt2a and Kdm5c in mice reverses dendritic spine deficits, behavioral traits including aggression, and partially corrects altered H3K4 methylation landscapes seen in each single mutant. Double-mutant mouse models, dendritic spine morphology, behavioral tests, H3K4me ChIP-seq, RNA-seq Communications biology Medium 32483278
2023 Menin-KMT2A interaction is a critical transcriptional dependency in KMT2A-rearranged and NPM1-mutant acute leukemia; pharmacological inhibition of menin-KMT2A interaction with revumenib induces leukemic differentiation and achieves remission in patients, establishing the menin–KMT2A protein–protein interaction as the functional oncogenic dependency. First-in-human phase 1 clinical trial with mechanistic correlatives (differentiation markers, residual disease clearance); prior preclinical menin-KMT2A inhibitor studies established the interaction Nature High 36922593 39121437
2023 Menin inhibition (loss of menin-KMT2A/B complex) paradoxically derepresses bivalent genes by redistributing KMT2A from active genes to bivalent promoters; a Menin-independent function of KMT2A/B maintains H3K4me3 and opposes polycomb-mediated repression at bivalent loci. Genome-wide CRISPR-Cas9 screens, pharmacological menin inhibition, H3K4me3/H3K27me3 ChIP-seq, genetic knockout in cancer cells and pluripotent stem cells Nature cell biology High 36635503
2024 JNJ-75276617 (bleximenib) inhibits the menin-KMT2A protein-protein interaction; a co-crystal structure of menin with JNJ-75276617 reveals a binding mode distinct from revumenib. Inhibition displaces the menin-KMT2A complex from target gene promoters (including MEIS1 and FLT3), reducing their expression. Co-crystal structure determination, chromatin immunoprecipitation-seq, gene expression analysis, in vitro antiproliferative assays, xenograft models Blood High 38905635
2019 KMT2A promotes colorectal cancer invasion and metastasis by transcriptionally activating cathepsin Z (CTSZ); p65 (NF-κB) recruits KMT2A to the CTSZ promoter, and knockdown of p65 reduces KMT2A occupancy at the CTSZ promoter. KMT2A knockdown in HCT116/DLD1 cells, in vivo xenograft metastasis model, ChIP assay showing p65 recruits KMT2A to CTSZ promoter Cancer medicine Medium 31090199
2017 KMT2A promotes melanoma cell growth by activating hTERT transcription; KMT2A knockdown reduces hTERT promoter activity and expression, and hTERT overexpression rescues the proliferation defect caused by KMT2A knockdown. KMT2A knockdown/overexpression in melanoma cell lines, hTERT promoter reporter assay, rescue experiment with hTERT overexpression, xenograft mouse model Cell death & disease Medium 28726783
2023 KMT2A promotes monocyte/macrophage expression of procoagulant (tissue factor, F3) and profibrinolytic factors (PLAU, PLAUR) and proinflammatory cytokines through NF-κB/RelA-dependent transcription; MLL1-dependent phenotypes were confirmed in a coronavirus infection model in vivo. Conditional MLL1 knockout in monocytes/macrophages using murine betacoronavirus MHVA59 model, in vitro NF-κB reporter assays, in vivo coagulation phenotype measurements, analysis of human SARS-CoV-2 positive samples Blood Medium 36493338
2024 KMT2A promotes expression of METTL3 via H3K4me3 modification; METTL3-mediated m6A modification then reduces ATG4a RNA stability, impairing autophagy in nucleus pulposus cells, which drives GATA4-dependent senescence and intervertebral disc degeneration. KMT2A and METTL3 silencing in nucleus pulposus cells, ChIP for H3K4me3 at METTL3 promoter, m6A-seq/MeRIP, ATG4a RNA stability assay, autophagic flux measurement, SASP quantification Bone research Medium 39572532
2024 An enhancer-derived lncRNA (Myrlin) physically interacts with the KMT2A/MLL1 complex and recruits it to the Myb locus; Myrlin CRISPRi reduces KMT2A occupancy at Myb, decreasing CDK9 and RNA Pol II binding and causing Pol II pausing in the Myb first exon/intron. CRISPR-Cas9 TSS deletion, CRISPRi, RNA immunoprecipitation showing Myrlin-KMT2A interaction, ChIP for KMT2A/CDK9/Pol II at Myb locus, 3C/chromosome conformation Cell reports Medium 38889007
2025 Loss of KMT2C/D in urothelium causes KMT2A-menin complex to redistribute from KMT2D-occupied enhancers to CpG-high and bivalent promoters, derepressing signal-induced immediate early genes; KMT2A-menin redistribution is a mechanistic consequence of KMT2C/D loss. Genetically engineered mouse models (Kmt2c/d knockout), ChIP-seq for KMT2A, H3K4me1, H3K27ac, nascent RNA transcription assays, functional differentiation and transformation assays Nature genetics High 39806204
2017 KMT2A missense variant p.Arg1154Trp (in the CXXC domain) causes disturbed subcellular distribution of KMT2A and alters expression of KMT2A target genes in patient fibroblasts; a variant in the transactivation domain (p.Met2853Arg) also alters target gene expression without affecting localization, demonstrating that both domains are functionally critical. Primary patient fibroblasts, immunofluorescence for subcellular localization, qRT-PCR for target gene expression European journal of human genetics Medium 29203834
2023 Proteasome inhibition in KMT2A-rearranged infant ALL depletes histone H2B monoubiquitination (H2Bub1) and histone H3K79 dimethylation at KMT2A target genes and downregulates the KMT2A gene expression signature, indicating proteasome inhibitors target the KMT2A transcriptional complex. Drug screen in primary KMT2Ar infant ALL specimens, ChIP analysis of H2Bub1 and H3K79me2, KMT2A target gene expression profiling Nature communications Medium 36781850

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature 411 36922593
1997 Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. The EMBO journal 355 9250666
1994 ALL-1 partial duplication in acute leukemia. Proceedings of the National Academy of Sciences of the United States of America 214 8016145
1998 The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Molecular and cellular biology 207 9418860
1997 A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins. Nature genetics 205 9207790
2023 The KMT2A recombinome of acute leukemias in 2023. Leukemia 182 37019990
1993 HRX involvement in de novo and secondary leukemias with diverse chromosome 11q23 abnormalities. Blood 182 8389614
2024 Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 173 39121437
1999 Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. Molecular and cellular biology 132 10490642
1993 A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias. Blood 129 8443374
1995 ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children. Blood 126 7756657
1994 A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene 118 8134107
1994 ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells. Blood 116 8080983
1995 The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. Blood 115 7662954
1997 HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. The Journal of biological chemistry 89 9353299
2022 Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell-like blasts in KMT2A-rearranged leukemia. Blood 86 34864916
2021 Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements. Blood cancer journal 86 34588432
2020 Recurrent YAP1 and KMT2A Gene Rearrangements in a Subset of MUC4-negative Sclerosing Epithelioid Fibrosarcoma. The American journal of surgical pathology 78 31592798
2017 KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions. Cell reports 74 28723559
2022 Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia. Nature medicine 67 35288693
1997 The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures. Blood 59 9129043
2024 Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias. Blood 56 38905635
2022 KMT2A: Umbrella Gene for Multiple Diseases. Genes 54 35328068
2015 Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium. International journal of cardiology 51 26322599
2023 Updates in KMT2A Gene Rearrangement in Pediatric Acute Lymphoblastic Leukemia. Biomedicines 48 36979800
2020 Mutually suppressive roles of KMT2A and KDM5C in behaviour, neuronal structure, and histone H3K4 methylation. Communications biology 44 32483278
2015 MPTP activates ASK1-p38 MAPK signaling pathway through TNF-dependent Trx1 oxidation in parkinsonism mouse model. Free radical biology & medicine 43 26164633
2023 Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes. Nature cell biology 40 36635503
1995 Involvement of the ALL-1 gene in a solid tumor. Proceedings of the National Academy of Sciences of the United States of America 38 7761425
2004 ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia. British journal of cancer 37 14970849
2019 Preparation and appraisal of self-assembled valsartan-loaded amalgamated Pluronic F127/Tween 80 polymeric micelles: Boosted cardioprotection via regulation of Mhrt/Nrf2 and Trx1 pathways in cisplatin-induced cardiotoxicity. Journal of drug targeting 36 31353972
1997 The localization of the HRX/ALL1 protein to specific nuclear subdomains is altered by fusion with its eps15 translocation partner. Cancer research 36 9041173
2025 Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed NPM1-Mutated or KMT2A-Rearranged AML. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35 40504618
2019 The stem cell-specific long noncoding RNA HOXA10-AS in the pathogenesis of KMT2A-rearranged leukemia. Blood advances 34 31867596
2017 Molecular and cellular issues of KMT2A variants involved in Wiedemann-Steiner syndrome. European journal of human genetics : EJHG 34 29203834
2024 Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation. Oncology and therapy 32 38300432
2022 Salidroside inhibited cerebral ischemia/reperfusion-induced oxidative stress and apoptosis via Nrf2/Trx1 signaling pathway. Metabolic brain disease 32 35976554
1994 Detection of HRX-FEL fusion transcripts in pre-pre-B-ALL with and without cytogenetic demonstration of t(4;11). Leukemia 32 7908708
2020 Down-regulation of DJ-1 Augments Neuroinflammation via Nrf2/Trx1/NLRP3 Axis in MPTP-induced Parkinson's Disease Mouse Model. Neuroscience 31 32526245
2019 KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation. Cancer medicine 31 31090199
1997 The structure of the human ALL-1/MLL/HRX gene. Leukemia & lymphoma 31 9477123
2017 KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway. Cell death & disease 29 28726783
1995 Partial duplication of HRX in acute leukemia with trisomy 11. Leukemia 29 7658717
2003 Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL(1). Leukemia 28 12682626
2023 Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study. Blood 27 37595275
2024 Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML. Blood 26 38096371
2024 KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m6A modification of ATG4a to promote NPCs senescence and IVDD progression. Bone research 26 39572532
2020 STVNa Attenuates Isoproterenol-Induced Cardiac Hypertrophy Response through the HDAC4 and Prdx2/ROS/Trx1 Pathways. International journal of molecular sciences 25 31968660
2024 KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives. International journal of molecular sciences 24 39201709
2020 Dexmedetomidine Protects against Myocardial Ischemia/Reperfusion Injury by Ameliorating Oxidative Stress and Cell Apoptosis through the Trx1-Dependent Akt Pathway. BioMed research international 24 33299886
2015 Trx1/TrxR1 system regulates post-selected DP thymocytes survival by modulating ASK1-JNK/p38 MAPK activities. Immunology and cell biology 23 25753394
2023 Protective effects of KLF4 on blood-brain barrier and oxidative stress after cerebral ischemia-reperfusion in rats through the Nrf2/Trx1 pathway. Cytokine 22 37441941
2020 Berberine alleviates pulmonary hypertension through Trx1 and β-catenin signaling pathways in pulmonary artery smooth muscle cells. Experimental cell research 22 32147507
2018 Redox-Inactive Peptide Disrupting Trx1-Ask1 Interaction for Selective Activation of Stress Signaling. Biochemistry 22 29261301
2024 Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia. International journal of molecular sciences 20 38892207
2021 Novel germline mutation KMT2A G3131S confers genetic susceptibility to familial myeloproliferative neoplasms. Annals of hematology 20 34228147
2020 KMT2A regulates cervical cancer cell growth through targeting VDAC1. Aging 19 32436862
2024 Detection of KMT2A Partial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes. Cancers 18 39766092
2024 Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia. Haematologica 17 39704147
2023 Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia. Nature communications 17 36781850
2023 Curdione inhibits ferroptosis in isoprenaline-induced myocardial infarction via regulating Keap1/Trx1/GPX4 signaling pathway. Phytotherapy research : PTR 17 37500597
2021 Ceramide induces the apoptosis of non‑small cell lung cancer cells through the Txnip/Trx1 complex. International journal of molecular medicine 17 33760130
2019 Up-regulation of antioxidative proteins TRX1, TXNL1 and TXNRD1 in the cortex of PTZ kindling seizure model mice. PloS one 17 30677045
2016 TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans. Genetics 17 26920757
1997 The human ALL-1/MLL/HRX antigen is predominantly localized in the nucleus of resting and proliferating peripheral blood mononuclear cells. Cancer research 17 9158002
2025 Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions. International journal of cancer 16 39887730
2024 YAP1::KMT2A-rearranged sarcomas harbor a unique methylation profile and are distinct from sclerosing epithelioid fibrosarcoma and low-grade fibromyxoid sarcoma. Virchows Archiv : an international journal of pathology 16 39641785
2022 Allelic complexity of KMT2A partial tandem duplications in acute myeloid leukemia and myelodysplastic syndromes. Blood advances 16 35584376
2022 Mutational landscape and clinical outcome of pediatric acute myeloid leukemia with 11q23/KMT2A rearrangements. Cancer medicine 16 35833755
2021 Hematopoietic stem cell transplantation for infants with high-risk KMT2A gene-rearranged acute lymphoblastic leukemia. Blood advances 16 34500465
2022 Novel Diagnostic and Therapeutic Options for KMT2A-Rearranged Acute Leukemias. Frontiers in pharmacology 15 35734412
2017 Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol-induced cardiac hypertrophy. Acta biochimica et biophysica Sinica 15 29036266
2025 Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters. Nature genetics 14 39806204
2025 Menin inhibitors in KMT2A-rearranged and NPM1-mutated acute leukemia: A scoping review of safety and efficacy. Critical reviews in oncology/hematology 14 40441466
2021 Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia. Cancers 14 34638301
2024 Hydrogen alleviates impaired lung epithelial barrier in acute respiratory distress syndrome via inhibiting Drp1-mediated mitochondrial fission through the Trx1 pathway. Free radical biology & medicine 13 38554812
2024 Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia. Cancer medicine 13 39428967
2023 The histone methyltransferase MLL1/KMT2A in monocytes drives coronavirus-associated coagulopathy and inflammation. Blood 13 36493338
2023 Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens. Proceedings of the National Academy of Sciences of the United States of America 13 37036970
2021 Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway. Biomolecules & therapeutics 13 33436533
2021 Drug Repurposing for Targeting Acute Leukemia With KMT2A (MLL)-Gene Rearrangements. Frontiers in pharmacology 13 34594227
2016 Thioredoxin (Trx1) regulates CD4 membrane domain localization and is required for efficient CD4-dependent HIV-1 entry. Biochimica et biophysica acta 13 27233453
1997 The FEL (AF-4) protein donates transcriptional activation sequences to Hrx-Fel fusion proteins in leukemias containing T(4;11)(Q21;Q23) chromosomal translocations. Leukemia research 13 9403001
2025 Precision medicine for high-risk gene fusions in pediatric AML: a focus on KMT2A, NUP98, and GLIS2 rearrangements. Blood 12 39808803
2024 Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia. Cancers 12 38730645
2023 Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway. Journal of neuroinflammation 12 36737785
2022 Expression of TRX1 optimizes the antitumor functions of human CAR T cells and confers resistance to a pro-oxidative tumor microenvironment. Frontiers in immunology 12 36591284
2020 Epigenetic regulation of protein translation in KMT2A-rearranged AML. Experimental hematology 11 32437908
2020 The KMT2A gene: mRNA differential expression in the ovary and a novel 13-nt nucleotide sequence variant associated with litter size in cashmere goats. Domestic animal endocrinology 11 32896800
1996 ALL-1 interacts with unr, a protein containing multiple cold shock domains. Oncogene 11 8934551
2025 Revumenib for Relapsed or Refractory Acute Leukemia With a KMT2A Translocation. The Annals of pharmacotherapy 10 40437770
2024 Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion. Blood advances 10 38029383
2024 The interaction between NLRP1 and oxidized TRX1 involves a transient disulfide bond. Cell chemical biology 10 38215746
2023 DNA fragility at the KMT2A/MLL locus: insights from old and new technologies. Open biology 10 36629017
2018 Dysregulated transcriptional networks in KMT2A- and MLLT10-rearranged T-ALL. Biomarker research 10 30159143
2015 Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation. Biochimica et biophysica acta 10 26410624
2025 Lactylation modulation identifies key biomarkers and therapeutic targets in KMT2A-rearranged AML. Scientific reports 9 39789150
2025 Outcomes of acute myeloid leukemia with KMT2A (MLL) rearrangement: a multicenter study of TROPHY group. Blood cancer journal 9 40316511
2024 An enhancer RNA recruits KMT2A to regulate transcription of Myb. Cell reports 9 38889007
2023 Combined BCL-2 and PI3K/AKT Pathway Inhibition in KMT2A-Rearranged Acute B-Lymphoblastic Leukemia Cells. International journal of molecular sciences 9 36674872

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