Affinage

AFF1

AF4/FMR2 family member 1 · UniProt P51825

Length
1210 aa
Mass
131.4 kDa
Annotated
2026-04-28
100 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AFF1 is a nuclear scaffolding protein that functions as a core subunit of the super elongation complex (SEC) and the AEP complex, coupling transcription initiation with elongation by constitutively associating with P-TEFb (CDK9/CycT) and recruiting the SL1 complex to load TBP onto RNA Pol II-dependent promoters (PMID:24367103, PMID:26593443). In complex with AF9, ENL, and AF10, AFF1 recruits Dot1 to promote histone H3-K79 methylation at elongating RNA Pol II, and its protein stability is controlled by Siah E3 ubiquitin ligase-mediated proteasomal degradation, while p300-dependent acetylation during genotoxic stress disrupts SEC assembly and inhibits global transcription (PMID:17135274, PMID:15459319, PMID:31611376). AFF1 is recurrently fused to MLL in t(4;11) acute leukemia, generating a constitutively active chimeric transcriptional activator that drives leukemogenesis through sustained AEP-dependent target gene expression (PMID:7689231, PMID:20153263). A missense mutation in Af4 causes progressive Purkinje cell degeneration and cerebellar ataxia in the robotic mouse, linked to dysregulated IGF-1 signaling (PMID:12629167, PMID:20007461).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 High

    Identification of AFF1 as a fusion partner of MLL in t(4;11) leukemia established the gene's relevance to hematopoietic malignancy and predicted it encodes a transcription factor based on its serine/proline-rich and glutamine-rich domains.

    Evidence Molecular cloning of the chromosomal breakpoint from the RS4;11 cell line with sequencing of the fusion open reading frame

    PMID:7689231

    Open questions at the time
    • No biochemical evidence for transcription factor activity yet
    • Mechanism of leukemic transformation by MLL-AF4 unknown
  2. 1995 High

    Demonstration that residues 480–560 of AF4 function as a potent transcriptional activation domain confirmed that AF4 is a bona fide transcriptional activator rather than merely a structural protein.

    Evidence GAL4 fusion reporter assay in yeast and mammalian cells with mutagenesis of the critical residues

    PMID:8618864

    Open questions at the time
    • Target genes and promoters unknown
    • Whether transactivation domain is required for leukemic transformation untested
  3. 2003 High

    Discovery that a missense mutation in Af4 causes progressive Purkinje cell loss and cerebellar ataxia in the robotic mouse revealed a critical non-hematopoietic function for AF4 in neuronal survival.

    Evidence ENU mutagenesis screen with genetic mapping, sequencing, and in situ hybridization showing Purkinje cell-specific expression

    PMID:12629167

    Open questions at the time
    • Molecular mechanism of Purkinje cell death unknown
    • Whether gain-of-function or loss-of-function drives degeneration unresolved
  4. 2004 High

    Identification of Siah-1a/Siah-2 as E3 ligases targeting Af4 for proteasomal degradation, and the finding that the robotic mutation reduces Siah binding and causes Af4 accumulation, established that AF4 protein levels are tightly controlled by ubiquitin-dependent turnover and that the robotic phenotype reflects gain-of-function through protein stabilization.

    Evidence Yeast two-hybrid, in vitro binding, co-immunoprecipitation, and transactivation assays comparing wild-type and mutant Af4

    PMID:15459319

    Open questions at the time
    • Ubiquitination sites on AF4 not mapped
    • Whether Siah-mediated degradation is regulated in specific cell types or conditions unknown
  5. 2004 Medium

    Demonstrating that AF4 and AF9 physically interact at discrete subnuclear foci provided the first evidence that these MLL fusion partners form a functional nuclear complex independent of MLL.

    Evidence Co-immunoprecipitation and confocal co-localization in transfected cells

    PMID:14603337

    Open questions at the time
    • Reciprocal endogenous Co-IP not shown
    • Other complex members not yet identified
    • Functional consequence of the AF4-AF9 interaction undefined
  6. 2006 High

    Establishing that Af4 positively regulates P-TEFb kinase activity and, together with Af9/Enl/Af10, recruits Dot1 to elongating Pol II for H3-K79 methylation unified the MLL fusion partners into a single transcription elongation pathway.

    Evidence In vitro kinase assays, luciferase reporters, ChIP for H3-K79me, immunoprecipitation, and analysis of the robotic mouse showing elevated phospho-Pol II and H3-K79me

    PMID:17135274

    Open questions at the time
    • Direct structural basis for P-TEFb activation by AF4 unknown
    • Whether AF4 complex operates genome-wide or at select loci unresolved
  7. 2009 High

    Identification of Igf-1 as a direct transcriptional target of the AF4 regulatory complex in Purkinje cells, with in vivo rescue by exogenous IGF-1, connected AF4's transcriptional function to a specific survival signaling pathway in the CNS.

    Evidence Laser capture microdissection with microarray, ChIP confirming direct Igf-1 binding, western blotting, and in vivo IGF-1 rescue of Purkinje cell death

    PMID:20007461

    Open questions at the time
    • Whether IGF-1 is the sole or primary mediator of Purkinje cell survival downstream of AF4 unclear
    • Mechanism by which excess AF4 reduces Igf-1 transcription not defined
  8. 2010 High

    Purification of the AEP complex (AF4, ENL, P-TEFb) and demonstration that MLL fusions to AEP components create constitutively active hybrid complexes provided the mechanistic basis for MLL-rearranged leukemogenesis.

    Evidence Affinity purification/mass spectrometry, ChIP at MLL target loci, and hematopoietic progenitor transformation assays

    PMID:20153263

    Open questions at the time
    • How AEP is normally recruited to and released from chromatin unknown
    • Relative contributions of AEP vs. DOT1L complex to leukemia not separated
  9. 2013 High

    Showing that AFF1 is a ubiquitous component of all major P-TEFb complexes (7SK snRNP, SEC, Brd4-P-TEFb) and that the CDK9-CycT-AFF1 trimer is transferred as a unit redefined AFF1 as a constitutive P-TEFb cofactor rather than a specialized elongation factor, and revealed its role in facilitating HIV Tat transactivation.

    Evidence Co-immunoprecipitation, mass spectrometry, in vitro P-TEFb extraction assays, and Tat transactivation reporter assays with AFF1 knockdown

    PMID:24367103

    Open questions at the time
    • Structural basis for AFF1's enhancement of Tat-CycT1 interaction unknown
    • Whether AFF1 and AFF4 are functionally redundant in all P-TEFb contexts unresolved
  10. 2015 High

    Discovery that the AF4 pSER domain recruits SL1 to load TBP onto Pol II promoters established a direct role for AF4 in transcription initiation, not just elongation, and identified TBP loading as the mechanism hijacked by MLL-AEP fusions.

    Evidence Co-immunoprecipitation of AF4 with SL1 subunits, ChIP for SL1/TBP recruitment, reporter assays, pSER mutagenesis, and dominant-negative SL1 experiments

    PMID:26593443

    Open questions at the time
    • How SL1 is repurposed from Pol I to Pol II promoters mechanistically unclear
    • Genome-wide scope of AF4-dependent TBP loading not characterized
  11. 2017 Medium

    Separation-of-function analyses established that AEP-dependent transcription activation and DOT1L-dependent transcriptional maintenance are cooperative but mechanistically distinct arms required for MLL fusion-driven leukemogenesis, and that AFF1 and AFF4 have non-redundant roles in osteogenic differentiation via distinct target promoters (DKK1 for AFF1, ID1 for AFF4).

    Evidence Separation-of-function MLL fusion constructs with transformation assays; siRNA knockdown with ChIP, ALP activity, and mineralization assays in mesenchymal stem cells

    PMID:28394257 PMID:28955517

    Open questions at the time
    • Structural basis for AFF1 vs. AFF4 promoter selectivity unknown
    • In vivo validation of AFF1-specific role in bone formation limited
  12. 2019 High

    Demonstrating that p300 acetylates AFF1 upon genotoxic stress, disrupting SEC assembly and impairing Pol II CTD phosphorylation, established a post-translational switch that converts AFF1 from an activator to a global transcriptional repressor in the DNA damage response.

    Evidence In vitro p300 acetylation assay, P-TEFb/CTD phosphorylation assay, Co-IP of SEC components, knockdown/rescue with acetylation-mimic mutants, ChIP-seq, and GRO-seq upon genotoxic stress

    PMID:31611376

    Open questions at the time
    • Identity of the acetylation sites on AFF1 and their individual contributions not fully dissected
    • Deacetylase(s) responsible for reversing this modification unknown
    • Whether acetylation also regulates AFF1 in non-genotoxic contexts untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for AFF1's scaffolding of SEC components, the rules governing AFF1 vs. AFF4 paralog selectivity at specific promoters, and the genome-wide scope of AF4-dependent TBP loading remain unresolved.
  • No high-resolution structure of AFF1 or SEC containing AFF1
  • Genome-wide ChIP-seq of endogenous AFF1 in normal (non-leukemic) cells limited
  • Relative contribution of AFF1 to P-TEFb regulation vs. AFF4 at the whole-transcriptome level unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1643685 Disease 4
Partners
AF10AF9CCNT1CDK9DDX6ENLSIAH1SIAH2
Complex memberships
7SK snRNP (as AFF1-P-TEFb subcomplex)AEP complex (AF4/ENL/P-TEFb)Super Elongation Complex (SEC)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 AFF1 (AF4) was identified as a fusion partner of MLL in t(4;11)(q21;q23) acute leukemia; AF4 encodes a serine- and proline-rich protein with a glutamine-rich carboxyl terminus, consistent with a transcription factor, and the MLL-AF4 chimeric protein was predicted to act through gain-of-function or dominant negative mechanisms. Molecular cloning of chromosomal breakpoint from RS4;11 cell line, sequencing of fusion transcript open reading frame Proceedings of the National Academy of Sciences of the United States of America High 7689231
1995 An AF4 polypeptide containing residues 480–560 functions as a transcriptional activation domain when fused to the GAL4 DNA-binding domain, identifying a strong transactivation region within AF4. GAL4 fusion reporter assay in yeast and mammalian cells; in vitro mutagenesis of the domain Proceedings of the National Academy of Sciences of the United States of America High 8618864
1997 Murine Af4 protein localizes to the nucleus, and the 5′ half of Af4 encodes a transcriptional transactivation domain; Af4 is expressed in hematopoietic, cardiovascular, skeletal, and CNS tissues and is downregulated upon B-lymphocyte differentiation. Nuclear localization by subcellular fractionation/immunofluorescence; transactivation assay; in situ hybridization for developmental expression Oncogene Medium 9365243
2003 A missense mutation in a highly conserved region of Af4 causes progressive, region-specific Purkinje cell loss and cerebellar ataxia in the robotic mouse; Af4 is specifically expressed in Purkinje cells, establishing a functional role for AF4 in CNS neuronal survival. ENU mutagenesis screen, genetic mapping, Sanger sequencing of mutation; in situ hybridization showing Purkinje cell-specific expression The Journal of neuroscience High 12629167
2004 AF4 and AF9 physically interact at discrete subnuclear foci ('AF4 bodies') that are non-nucleolar; the MLL-AF4 fusion protein retains this interaction and alters AF9 subnuclear localization. Co-immunoprecipitation, confocal microscopy co-localization, expression of MLL-AF4 fusion to assess localization changes Leukemia Medium 14603337
2004 Af4 protein is targeted for proteasomal degradation by binding to E3 ubiquitin ligases Siah-1a and Siah-2; the robotic mouse mutation in Af4 reduces its binding affinity to Siah-1a, causing Af4 accumulation and increased transcriptional activity. This Siah-binding/degradation mechanism is conserved across all AFF family members. Yeast two-hybrid screen; in vitro binding assays; co-immunoprecipitation; transactivation assays comparing wild-type vs. mutant Af4 Proceedings of the National Academy of Sciences of the United States of America High 15459319
2006 Mouse Af4 positively regulates P-TEFb (CDK9/cyclin T) kinase activity and, in a complex with Af9, Enl, and Af10, recruits Dot1 to elongating RNA Pol II to mediate histone H3-K79 methylation. P-TEFb-dependent phosphorylation of Af4, Af9, and Enl controls their transactivation activity and/or protein stability, and these pathways are interconnected. In vitro kinase assays; luciferase reporter transcription assays; ChIP for H3-K79 methylation; immunoprecipitation of complexes; robotic mouse as overexpression model showing elevated phospho-Pol II and H3-K79 methylation Human molecular genetics High 17135274
2009 AF4 directly regulates the IGF-1 signaling pathway in Purkinje cells; chromatin immunoprecipitation confirmed Igf-1 as a direct transcriptional target of the AF4 regulatory complex, and Af4 accumulation in robotic PCs correlates with decreased Igf-1 expression, reduced IGF-1R and ERK1/2 activation, and Purkinje cell death preventable by exogenous IGF-1 treatment. Laser capture microdissection + microarray of robotic vs. wild-type Purkinje cells; chromatin immunoprecipitation (ChIP) confirming direct Igf-1 target; western blotting for downstream signaling; in vivo IGF-1 rescue experiment The Journal of neuroscience High 20007461
2010 AF4, ENL family proteins, and P-TEFb form a higher-order complex (AEP) that is normally recruited to MLL-target chromatin to facilitate transcription elongation. MLL oncoproteins fused to AEP components constitutively form hybrid MLL/AEP complexes causing sustained target gene expression. Affinity purification/mass spectrometry of AF4/ENL complexes; ChIP at MLL target loci; hematopoietic progenitor transformation assays; co-immunoprecipitation Cancer cell High 20153263
2011 AFF1/AF4 localizes to the nucleus and can bind RNA, with high apparent affinity for G-quadruplex RNA structures. Like other AFF family members, overexpression of AFF1 interferes with the organization/biogenesis of nuclear speckles. Subcellular localization by immunofluorescence; RNA-binding assays including G-quadruplex binding; nuclear speckle analysis by immunofluorescence following overexpression Human molecular genetics Medium 21330300
2012 AF4 promotes CD133 (PROM1) transcription; RNAi knockdown of AF4 dramatically reduces CD133 transcript levels in multiple cancer cell lines, and CD133 is required for MLL-AF4-dependent ALL cell survival. Parallel genome-wide RNAi screens; AF4 knockdown with qRT-PCR for CD133; CD133 knockdown with cell viability assay Cancer research Medium 22337994
2013 AFF1 is a ubiquitous component of P-TEFb complexes, including 7SK snRNP, super elongation complexes (SECs), and the Brd4-P-TEFb complex; the tripartite CDK9-CycT-AFF1 complex is transferred as a unit within the P-TEFb network. AFF1 increases the affinity of HIV Tat for CycT1, facilitating Tat's extraction of P-TEFb from 7SK snRNP and formation of Tat-SECs required for full HIV transactivation. Co-immunoprecipitation; mass spectrometry; in vitro P-TEFb extraction assays; Tat transactivation reporter assays; AFF1 knockdown Proceedings of the National Academy of Sciences of the United States of America High 24367103
2015 The pSER domain of AF4 family proteins associates with SL1 (a core RNAP1 pre-initiation complex component) on chromatin, loading TBP onto the promoter to initiate RNAP2-dependent transcription; this mechanism is hijacked by MLL-AEP fusion proteins for constitutive target gene activation. Co-immunoprecipitation of AF4 with SL1 subunits; ChIP showing SL1 and TBP recruitment; reporter assays; mutagenesis of pSER domain; dominant-negative SL1 subunit experiments Nature communications High 26593443
2016 TBP loading by AF4 through the SL1 complex is the major rate-limiting step in MLL fusion-dependent transcription; this activity, rather than mediator recruitment or transcriptional elongation, is responsible for the oncogenic transcriptional output of MLL-AEP fusion proteins. Separation-of-function mutant analysis in transcription reporter assays; rescue experiments with AF4 mutants lacking specific activities (mediator binding, elongation vs. TBP loading) Cell cycle Medium 27564129
2016 DDX6 (a DEAD-box RNA helicase) binds to 7SK snRNA and transfers P-TEFb to the AF4/AFF1 super elongation complex; DDX6 stably binds AF4 (demonstrated by GST pull-down and Co-IP), and co-overexpression of AF4 and DDX6 synergistically increases cellular mRNA production. GST pull-down; co-immunoprecipitation; mRNA quantification upon overexpression and knockdown of DDX6 and AF4 American journal of blood research Medium 27679741
2017 AFF1 and AFF4 differentially regulate osteogenic differentiation of human mesenchymal stem cells; AFF1 depletion increases osteogenesis, while AFF4 depletion inhibits it. Mechanistically, AFF1 binds the DKK1 promoter and regulates its expression, whereas AFF4 is enriched at the ID1 promoter and regulates BMP2 signaling. siRNA knockdown with ALP activity assay, mineralization assay, gene expression; ChIP showing AFF1 binding to DKK1 promoter and AFF4 to ID1 promoter; BRE luciferase reporter; in vivo bone formation assay Bone research Medium 28955517
2017 AF4-containing AEP complex and the DOT1L complex cooperatively activate transcription in MLL-rearranged leukemia; constitutive AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance together are required for full leukemic transformation of hematopoietic progenitors. Separation-of-function MLL fusion constructs; hematopoietic progenitor transformation assays; gene expression analysis; pharmacological inhibition of individual pathways The Journal of clinical investigation Medium 28394257
2019 AFF1 is acetylated by the acetyltransferase p300 at specific sites upon genotoxic stress; this acetylation reduces AFF1 interaction with other SEC components and impairs P-TEFb-mediated CTD phosphorylation of RNA Pol II, leading to global transcriptional inhibition. An acetylation-mimic mutant cannot restore SEC recruitment or target gene expression, while wild-type AFF1 can. In vitro acetylation assay with p300; in vitro P-TEFb/CTD phosphorylation assay; co-immunoprecipitation of SEC components; AFF1 knockdown/rescue with wild-type vs. acetylation-mimic mutant; ChIP-seq; global run-on sequencing upon genotoxic stress Proceedings of the National Academy of Sciences of the United States of America High 31611376

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer cell 436 18977325
2010 A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer cell 304 20153263
2002 Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet (London, England) 274 12114041
2006 The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Human molecular genetics 259 17135274
1993 Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I. Proceedings of the National Academy of Sciences of the United States of America 236 8356062
1993 Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proceedings of the National Academy of Sciences of the United States of America 235 7689231
2014 A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM. Analytical and bioanalytical chemistry 135 25084738
2010 The AF4.MLL fusion protein is capable of inducing ALL in mice without requirement of MLL.AF4. Blood 125 20194896
1995 Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia. Proceedings of the National Academy of Sciences of the United States of America 121 8618864
2013 RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell reports 117 23352661
2012 A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese. PLoS genetics 103 22291604
1999 Purified natural and recombinant Fel d 1 and cat albumin in in vitro diagnostics for cat allergy. The Journal of allergy and clinical immunology 102 10589005
1996 Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. International immunology 97 8982778
1998 Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation. Blood 96 9680349
2006 A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy. Blood 95 16551973
2005 The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy 91 16134993
2015 Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia. Blood 90 26463423
2017 MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia. Oncogene 87 28114278
1986 Dose of cat (Felis domesticus) allergen 1 (Fel d 1) that induces asthma. The Journal of allergy and clinical immunology 85 3722635
2005 Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-gamma+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 84 15649266
1993 Detection of ALL-1/AF4 fusion transcript by reverse transcription-polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation. Blood 84 8219184
2011 A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS. The Journal of allergy and clinical immunology 82 21411130
2006 A conditional model of MLL-AF4 B-cell tumourigenesis using invertor technology. Oncogene 79 16607274
2009 The major cat allergen, Fel d 1, in diagnosis and therapy. International archives of allergy and immunology 76 19844127
2005 Targeting MLL-AF4 with short interfering RNAs inhibits clonogenicity and engraftment of t(4;11)-positive human leukemic cells. Blood 75 16046533
1994 The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in t(4;11)(q21;q23)-containing acute lymphoblastic leukemia. Blood 75 8286732
2004 MLL fusion partners AF4 and AF9 interact at subnuclear foci. Leukemia 74 14603337
2013 AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation. Proceedings of the National Academy of Sciences of the United States of America 66 24367103
2011 Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability. Human molecular genetics 66 21330300
2003 Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli. The Journal of biological chemistry 66 12732623
2017 MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia. Cell reports 65 28076791
2017 Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia. The Journal of clinical investigation 58 28394257
2003 A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 12629167
2006 Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+ T cells. The Journal of allergy and clinical immunology 56 17137868
1996 Definition of the human T-cell epitopes of Fel d 1, the major allergen of the domestic cat. The Journal of allergy and clinical immunology 54 8939151
2010 Insights into the cellular origin and etiology of the infant pro-B acute lymphoblastic leukemia with MLL-AF4 rearrangement. Leukemia 53 21135858
2022 Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia. Blood 52 35839448
1994 IgE epitopes on the cat (Felis domesticus) major allergen Fel d I: a study with overlapping synthetic peptides. The Journal of allergy and clinical immunology 49 7508463
2020 H3K79me2/3 controls enhancer-promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells. Leukemia 45 32242051
2012 A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification. Cell research 45 22212479
2015 Dendritic cell-derived exosomes carry the major cat allergen Fel d 1 and induce an allergic immune response. Allergy 44 26198793
2015 AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription. Nature communications 44 26593443
2016 The cat lipocalin Fel d 7 and its cross-reactivity with the dog lipocalin Can f 1. Allergy 43 27289080
2001 Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 43 11529899
1993 Recombinant Fel d.I: Expression, purification, IgE binding and reaction with cat-allergic human T cells. Molecular immunology 43 8487777
2002 LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia. Genes, chromosomes & cancer 42 12203795
1975 Segregation of RD-114 AND FeL-V-related sequences in crosses between domestic cat and leopard cat. Nature 42 170535
2012 The mixed lineage leukemia (MLL) fusion-associated gene AF4 promotes CD133 transcription. Cancer research 41 22337994
2009 DNA copy-number abnormalities do not occur in infant ALL with t(4;11)/MLL-AF4. Leukemia 41 19907438
2017 AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs. Bone research 39 28955517
2014 Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL leukemias through MLL-AF4. Cancer cell 39 24735925
2021 The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis. Leukemia 38 34321607
2016 Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development. Cell reports 38 27396339
2010 Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by controlling expression of the telomerase subunit TERT. Leukemia 38 20686504
2007 Complex MLL rearrangements in t(4;11) leukemia patients with absent AF4.MLL fusion allele. Leukemia 37 17410185
2004 Mediation of Af4 protein function in the cerebellum by Siah proteins. Proceedings of the National Academy of Sciences of the United States of America 37 15459319
2003 Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23). Oncogene 37 12743608
2021 Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL-AF4 fusion protein. Scientific reports 34 34035431
1994 Detection of HRX-FEL fusion transcripts in pre-pre-B-ALL with and without cytogenetic demonstration of t(4;11). Leukemia 32 7908708
2014 Hypoallergenic derivatives of Fel d 1 obtained by rational reassembly for allergy vaccination and tolerance induction. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 31 24552249
1994 Molecular analysis of MLL-1/AF4 recombination in infant acute lymphoblastic leukemia. Leukemia 30 8152249
2013 FLT3 activation cooperates with MLL-AF4 fusion protein to abrogate the hematopoietic specification of human ESCs. Blood 29 23479570
2004 Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein. Leukemia 29 14990976
2003 Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome. Blood 29 12791662
1998 Complement-inhibiting cucurbitacin glycosides from Picria fel-terrae. Journal of natural products 29 9644059
2002 High-level expression of immunoreactive recombinant cat allergen (Fel d 1): Targeting to antigen-presenting cells. The Journal of allergy and clinical immunology 27 12417885
2021 miR-130b and miR-128a are essential lineage-specific codrivers of t(4;11) MLL-AF4 acute leukemia. Blood 26 34111240
2017 The full transforming capacity of MLL-Af4 is interlinked with lymphoid lineage commitment. Blood 25 28637661
2016 Analysis of β-glucan molar mass from barley malt and brewer's spent grain with asymmetric flow field-flow fractionation (AF4) and their association to proteins. Carbohydrate polymers 25 27987960
2014 Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wild-type MLL. Oncogenesis 25 25402609
2013 MicroRNA-142-3p inhibits cell proliferation in human acute lymphoblastic leukemia by targeting the MLL-AF4 oncogene. Molecular biology reports 25 24057258
2020 The Major Cat Allergen Fel d 1 Binds Steroid and Fatty Acid Semiochemicals: A Combined In Silico and In Vitro Study. International journal of molecular sciences 24 32085519
2001 Breakpoints of t(4;11) translocations in the human MLL and AF4 genes in ALL patients are preferentially clustered outside of high-affinity matrix attachment regions. Journal of cellular biochemistry 24 11527155
1996 Human T and B cell immune responses to Fel d 1 in cat-allergic and non-cat-allergic subjects. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 24 8955581
2021 HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis. eLife 23 34431785
2019 Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4. Scientific reports 23 30728436
2016 MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylation. Experimental hematology 23 27856324
2013 Ligand-independent FLT3 activation does not cooperate with MLL-AF4 to immortalize/transform cord blood CD34+ cells. Leukemia 23 24240202
1997 Expression of BCR-ABL, E2A-PBX1, and MLL-AF4 fusion transcripts in newly diagnosed children with acute lymphoblastic leukemia: a Children's Cancer Group initiative. Leukemia & lymphoma 23 9250788
2021 A KMT2A-AFF1 gene regulatory network highlights the role of core transcription factors and reveals the regulatory logic of key downstream target genes. Genome research 22 34088716
2016 Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine. PloS one 22 26954254
2016 TBP loading by AF4 through SL1 is the major rate-limiting step in MLL fusion-dependent transcription. Cell cycle (Georgetown, Tex.) 22 27564129
2022 Evolutionary Biology and Gene Editing of Cat Allergen, Fel d 1. The CRISPR journal 21 35343817
2010 t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. Leukemia research 21 20869771
2007 The AF4-mimetic peptide, PFWT, induces necrotic cell death in MV4-11 leukemia cells. Leukemia research 21 17875318
2011 AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice. Blood 20 22025528
2009 AF4 is a critical regulator of the IGF-1 signaling pathway during Purkinje cell development. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 20007461
2008 Identification of an immunodominant region of Fel d 1 and characterization of constituent epitopes. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20 19489916
2005 The robotic mouse: unravelling the function of AF4 in the cerebellum. Cerebellum (London, England) 20 16321881
1997 Cloning and developmental expression of the murine homolog of the acute leukemia proto-oncogene AF4. Oncogene 20 9365243
1992 Structure of the major cat allergen Fel d I in different allergen sources: an immunoblotting analysis with monoclonal antibodies against denatured Fel d I and human IgE. International archives of allergy and immunology 20 1282843
2016 DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex. American journal of blood research 19 27679741
2016 Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis. Scientific reports 19 27698462
2021 REGN1908-1909 monoclonal antibodies block Fel d 1 in cat allergic subjects: Translational pharmacokinetics and pharmacodynamics. Clinical and translational science 18 34437752
2019 Matrix-dependent size modifications of iron oxide nanoparticles (Ferumoxytol) spiked into rat blood cells and plasma: Characterisation with TEM, AF4-UV-MALS-ICP-MS/MS and spICP-MS. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 18 31284093
2019 AFF1 acetylation by p300 temporally inhibits transcription during genotoxic stress response. Proceedings of the National Academy of Sciences of the United States of America 18 31611376
2015 HMGA2 as a potential molecular target in KMT2A-AFF1-positive infant acute lymphoblastic leukaemia. British journal of haematology 18 26403224
2013 Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations. Cancer genetics 18 23859904
2011 Resistance of MLL-AFF1-positive acute lymphoblastic leukemia to tumor necrosis factor-alpha is mediated by S100A6 upregulation. Blood cancer journal 18 22829076
2012 Association of AFF1 rs340630 and AFF3 rs10865035 polymorphisms with systemic lupus erythematosus in a Chinese population. Immunogenetics 17 22983539