Affinage

Showing AFF1 — AF4 is a alias.

AFF1

AF4/FMR2 family member 1 · UniProt P51825

Length
1210 aa
Mass
131.4 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AFF1 (AF4) is a nuclear scaffolding subunit of the super elongation complex (SEC) that drives RNA polymerase II transcriptional elongation (PMID:21030982, PMID:24367103). Originally identified as the serine/proline-rich, glutamine-rich putative transcription factor fused to MLL by the t(4;11) translocation (PMID:1423625, PMID:7689231), AFF1 was established as a bona fide transcriptional activator through its autonomous transactivation domain (PMID:8555498) and localizes to discrete subnuclear foci ('AF4 bodies') where it co-localizes with the chromatin reader AF9 (PMID:9808577, PMID:14603337). AFF1 constitutively binds the P-TEFb kinase (CDK9-CycT) and is a ubiquitous component of the P-TEFb network, partitioning among the 7SK snRNP, SECs, and Brd4-P-TEFb complexes; the tripartite CDK9-CycT-AFF1 module is transferred as a unit, and AFF1 stimulates P-TEFb kinase activity to phosphorylate the Pol II CTD and release promoter-arrested polymerase (PMID:21030982, PMID:24367103). Within an AF4/AF9/ENL/AF10 assembly it recruits the H3K79 methyltransferase DOT1L to elongating Pol II, coupling elongation to chromatin modification (PMID:17135274, PMID:18977325, PMID:21030982). AFF1 activates specific target promoters by direct binding, including Igf-1 in cerebellar Purkinje cells (PMID:20007461), CD133/PROM1 (PMID:22337994), and DKK1 in mesenchymal stem cells where it restrains osteogenic differentiation (PMID:28955517). Its dosage and activity are tightly controlled: SIAH1/SIAH2 E3 ubiquitin ligases bind the AFF1 N-terminus to direct proteasomal turnover (PMID:15221006, PMID:15459319), and p300-mediated acetylation transiently disrupts SEC assembly and dampens Pol II CTD phosphorylation during genotoxic stress (PMID:31611376). A missense mutation reducing SIAH-mediated degradation stabilizes Af4, elevates its transcriptional output, and causes autosomal dominant cerebellar ataxia with Purkinje cell loss in mice (PMID:12629167, PMID:15459319). In t(4;11) leukemia, the MLL-AF4 fusion redirects these elongation and H3K79-methylation activities to hematopoietic loci, and disruption of the AF4-AF9 interaction selectively kills MLL-AF4 leukemic cells (PMID:15269783, PMID:18977325, PMID:34431785).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1992 High

    Established the molecular identity of AFF1 by cloning the t(4;11) breakpoint, defining it as the MLL fusion partner and a candidate transcription factor.

    Evidence Molecular cloning and breakpoint sequencing of the t(4;11) translocation

    PMID:1423625 PMID:7689231

    Open questions at the time
    • Putative transcription factor status inferred from sequence motifs, not demonstrated biochemically
    • No direct target genes identified
  2. 1996 Medium

    Demonstrated that AFF1 possesses an autonomous transactivation domain retained in MLL-AF4, converting it from a putative to a functional transcriptional activator.

    Evidence GAL4-fusion transactivation reporter assay and DNA-cellulose binding in mammalian cells

    PMID:8555498

    Open questions at the time
    • Reporter-based activity does not identify endogenous promoter targets
    • Mechanism of activation unknown
  3. 1997 Medium

    Confirmed nuclear localization of the endogenous AFF1 protein and defined conserved domains shared across the AF4/LAF4/FMR2 family.

    Evidence Polyclonal antibody Western blotting and immunofluorescence in human and murine cells

    PMID:9233580 PMID:9365243

    Open questions at the time
    • No interacting partners identified
    • Functional role of conserved domains not tested
  4. 1998 Medium

    Localized AFF1 to discrete subnuclear foci and detected an associated 45-kDa protein, hinting at a defined nuclear complex.

    Evidence Confocal immunofluorescence and immunoprecipitation in leukemic cell lines

    PMID:9808577

    Open questions at the time
    • Identity of the co-precipitating 45-kDa protein not determined
    • Functional significance of foci unknown
  5. 2003 High

    Linked AFF1 dosage to neuronal maintenance, showing a missense mutation in conserved Af4 causes dominant cerebellar ataxia and Purkinje cell loss.

    Evidence ENU mutagenesis, genetic mapping, and in situ hybridization in mouse

    PMID:12629167

    Open questions at the time
    • Molecular basis of the gain/loss of function not yet resolved at this stage
    • Downstream target genes in Purkinje cells unidentified
  6. 2004 Medium

    Defined the AFF1 regulatory and partner network: SIAH1/2 control its proteasomal turnover, and AF9 binds at subnuclear foci, with the AF9 interaction being a selective vulnerability in MLL-AF4 leukemia.

    Evidence Yeast two-hybrid, reciprocal co-IP, degradation and growth-transformation assays, peptide disruption of AF4-AF9

    PMID:14603337 PMID:15221006 PMID:15269783

    Open questions at the time
    • Functional consequence of AF4-AF9 binding for transcription not yet shown
    • Single-lab findings without reciprocal structural validation
  7. 2004 High

    Connected SIAH-mediated degradation to control of AFF1 transcriptional output, explaining the ataxia mutant as a stabilized, hyperactive protein.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, degradation and transcription assays in mouse brain

    PMID:15459319

    Open questions at the time
    • Direct neuronal target genes not yet identified
    • Whether degradation operates on SEC-assembled AFF1 unknown
  8. 2006 High

    Placed AFF1 mechanistically at the heart of elongation control, as a positive regulator of P-TEFb that recruits DOT1L for H3K79 methylation within an AF9/ENL/AF10 complex.

    Evidence Luciferase reporter, co-IP, ChIP, phospho-Pol II and H3K79me immunoblots, robotic mouse analysis

    PMID:17135274

    Open questions at the time
    • Stoichiometry and assembly order of the complex not resolved
    • Direct vs indirect stimulation of P-TEFb not separated
  9. 2008 High

    Validated the elongation/chromatin axis in leukemia, showing MLL-AF4-driven H3K79 methylation and DOT1L-dependent activation of critical target genes.

    Evidence ChIP-chip of H3K79me, DOT1L inhibition, and expression profiling in leukemia models

    PMID:18977325

    Open questions at the time
    • Direct AFF1 binding at individual targets not all mapped
    • Mechanism of locus selectivity unknown
  10. 2009 High

    Identified Igf-1 as a direct AFF1 target whose loss underlies Purkinje cell death, providing an in vivo rescue link between AFF1 transcription and neuronal survival.

    Evidence Laser-capture microarray, ChIP, and IGF-1 rescue in robotic mice

    PMID:20007461

    Open questions at the time
    • Whether Igf-1 is the sole relevant target unclear
    • SEC requirement at the Igf-1 promoter not tested
  11. 2010 High

    Biochemically defined the AFF1 and AF4-MLL complexes, identifying P-TEFb and chromatin-modifying enzymes and demonstrating activation of arrested Pol II in vitro.

    Evidence Affinity purification, mass spectrometry, and in vitro Pol II elongation assay

    PMID:21030982

    Open questions at the time
    • Functional contribution of each of the 16 fusion-complex constituents not dissected
    • Native complex architecture not solved structurally
  12. 2012 Medium

    Extended AFF1's direct target repertoire to CD133/PROM1, a gene required for MLL-AF4+ leukemia cell survival.

    Evidence RNAi screen, siRNA knockdown, qPCR, and viability assays across cancer lines

    PMID:22337994

    Open questions at the time
    • Direct promoter occupancy by ChIP not shown here
    • Single-lab finding
  13. 2013 High

    Established AFF1 as a ubiquitous P-TEFb network hub that licenses Tat-dependent HIV transcription by promoting P-TEFb extraction from 7SK snRNP.

    Evidence Co-IP, affinity purification, in vitro P-TEFb extraction, and HIV transactivation reporter

    PMID:24367103

    Open questions at the time
    • Structural basis of CDK9-CycT-AFF1 tripartite assembly not resolved
    • Regulation of AFF1 partitioning between complexes unknown
  14. 2016 Medium

    Identified DDX6 as a factor that feeds P-TEFb from 7SK snRNA into the AFF1 SEC and stably binds AFF1 to boost mRNA output.

    Evidence GST pull-down, co-IP, and mRNA production assays with knockdown

    PMID:27679741

    Open questions at the time
    • Direct vs indirect AFF1-DDX6 contact not structurally defined
    • Single-lab finding in a low-circulation venue
  15. 2017 High

    Defined an AFF1-DKK1 regulatory axis controlling mesenchymal stem cell osteogenesis, broadening AFF1's physiological roles beyond leukemia and neurons.

    Evidence siRNA knockdown, ChIP at the DKK1 promoter, epistasis rescue, and in vivo bone formation assay

    PMID:28955517

    Open questions at the time
    • SEC dependence at the DKK1 promoter not tested
    • Upstream signals regulating AFF1 in MSCs unknown
  16. 2019 High

    Revealed acetylation as a post-translational switch: p300 acetylates AFF1 to disassemble the SEC and globally dampen elongation during genotoxic stress.

    Evidence In vitro acetylation and CTD kinase assays, mutagenesis, co-IP, ChIP, and rescue

    PMID:31611376

    Open questions at the time
    • Deacetylase reversing the modification not identified
    • Selectivity of stress-induced downregulation across loci unclear
  17. 2021 Medium

    Mapped how AFF1-containing AEP/SEC is recruited to chromatin, showing the ELL C-terminus provides an AF4-binding platform regulated by the HBO1 complex.

    Evidence Co-IP, ChIP-seq, domain mapping, and murine leukemia transformation assays

    PMID:34431785

    Open questions at the time
    • Generality beyond hematopoietic progenitors untested
    • Competition between EAF1 and AEP not quantitatively resolved
  18. 2022 Medium

    Showed that under stress AFF1 SEC reassembles active P-TEFb from monomerized CDK9 and CycT1 on chromatin, providing a recovery mechanism for elongation.

    Evidence Co-IP under stress, CDK9 T186 phosphorylation, and chromatin fractionation

    PMID:34935961

    Open questions at the time
    • In vivo physiological context of reassembly not established
    • Single-lab biochemical study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AFF1 SEC achieves locus selectivity, and what structural arrangement governs the CDK9-CycT-AFF1 module and its competing post-translational controls, remains unresolved.
  • No high-resolution structure of the AFF1 SEC
  • Mechanism directing AFF1 to specific target promoters genome-wide unknown
  • Interplay of phosphorylation, acetylation, and SIAH-mediated turnover not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AF9CCNT1CDK9DDX6DOT1LEP300SIAH1SIAH2
Complex memberships
AF4/ENL/P-TEFb (AEP) complexMLL-AF4 fusion complexP-TEFb (CDK9-CycT)super elongation complex (SEC)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 The t(4;11) chromosomal translocation fuses the ALL-1 (MLL) gene to the AF-4 (AFF1) gene on chromosome 4, generating a chimeric protein. AF-4 was identified as a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. Molecular cloning, breakpoint sequencing, open reading frame analysis Cell High 1423625
1993 The MLL-AF4 fusion protein (der(11) product) retains the AF4 transactivation domain. AF4 was characterized as a serine-proline-rich putative transcription factor with nuclear localization and GTP-binding motifs in the portion retained in the fusion. Molecular cloning of fusion transcript, sequence analysis of complete open reading frame Proceedings of the National Academy of Sciences of the United States of America High 7689231
1996 AF4 protein has a domain that activates transcription when fused to the GAL4 DNA-binding domain, establishing AF4 as a transcriptional activator. The AF4 transactivation domain is retained in the MLL/AF4 fusion protein. GAL4-fusion transactivation assay in mammalian cells; double-stranded DNA cellulose binding assay Blood Medium 8555498
1997 The AF-4 protein (116 kDa) is localized predominantly to the nucleus in mitogen-stimulated human peripheral blood mononuclear cells, consistent with its role as a nuclear transcription factor. The gene contains five highly conserved domains shared with LAF-4 and FMR-2 family members. Polyclonal antibody production, Western blotting, immunofluorescence localization British journal of haematology Medium 9233580
1997 The murine Af4 protein localizes to the nucleus and encodes a region in its 5' half with transcriptional transactivation activity, which is disrupted by the t(4;11) translocation in human leukemias. Nuclear localization by immunofluorescence; transactivation assay Oncogene Medium 9365243
1998 AF4 protein (125 kDa and 145 kDa isoforms) localizes to discrete subnuclear punctate compartments by confocal immunofluorescence in both t(4;11) and non-t(4;11) leukemic cells. A 45-kDa protein co-precipitates with AF4. The MLL-AF4 fusion protein (240 kDa) shows a similar subnuclear distribution as wild-type AF4. Western blotting with specific antibodies, immunoprecipitation, confocal immunofluorescence microscopy Blood Medium 9808577
2001 Drosophila Lilliputian (lilli), the AF4/FMR2 family ortholog, functions in the Ras/MAPK pathway for cell identity determination and is essential for normal cellular growth. Loss of Lilli autonomously reduces cell size and partially suppresses growth increases from PTEN loss, placing AF4-family proteins in parallel with Ras/MAPK and PI3K/PKB pathways. Drosophila genetic epistasis, suppressor analysis with activated Raf and PTEN mutants, clonal analysis Development (Cambridge, England) Medium 11171403
2003 A missense mutation in the highly conserved region of mouse Af4 causes autosomal dominant cerebellar ataxia with region-specific Purkinje cell loss. Af4 is specifically expressed in Purkinje cells, establishing a direct role for Af4 in cerebellar neuronal maintenance. ENU mutagenesis screen, genetic mapping, in situ hybridization for Af4 in Purkinje cells The Journal of neuroscience High 12629167
2004 AF4 and AF9 interact at discrete subnuclear foci termed 'AF4 bodies'. This interaction is maintained by the MLL-AF4 fusion protein, and MLL-AF4 expression alters the subnuclear localization of AF9. Co-immunoprecipitation, confocal immunofluorescence co-localization, co-transfection Leukemia Medium 14603337
2004 AF4 wild-type protein and the AF4.MLL fusion protein interact with E3 ubiquitin ligases SIAH1 and SIAH2 via the N-terminal portion of AF4, and this interaction protects AF4.MLL from proteasomal degradation, contributing to growth transformation. Yeast two-hybrid screening, co-immunoprecipitation, proteasome degradation assay, growth transformation assay Oncogene Medium 15221006
2004 A synthetic peptide (PFWT) based on the AF9-binding domain of AF4 disrupts the AF4-AF9 protein interaction in vitro and in vivo, and inhibits proliferation/induces apoptosis specifically in t(4;11) leukemia cells expressing MLL-AF4. Peptide competition assay, cell proliferation assay, apoptosis assay, co-immunoprecipitation disruption Leukemia Medium 15269783
2004 Af4 binds E3 ubiquitin ligases Siah-1a and Siah-2 in the brain (identified by yeast two-hybrid). The robotic mutant Af4 shows significantly reduced affinity for Siah-1a, leading to near-complete abolition of mutant Af4 proteasomal degradation and accumulation of Af4 in Purkinje cells. Mutant Af4 has increased transcriptional activity relative to wild-type, indicating that Siah-mediated degradation controls Af4 transcriptional activity levels. Yeast two-hybrid screen, in vitro binding assays, co-immunoprecipitation, mammalian transcriptional activity assay, Siah-1a degradation assay Proceedings of the National Academy of Sciences of the United States of America High 15459319
2006 Mouse Af4 functions as a positive regulator of P-TEFb kinase activity and, in complex with MLL fusion partners Af9, Enl, and Af10, mediates histone H3-K79 methylation by recruiting Dot1 to elongating RNA Pol II. P-TEFb-dependent phosphorylation of Af4, Af9, and Enl controls their transactivation activity and/or protein stability. Increased phosphorylated Pol II and methylated H3-K79 are observed in the ataxic robotic mouse (Af4 overexpression model). Reporter gene assay (luciferase), co-immunoprecipitation, ChIP, immunoblot for phospho-Pol II and H3-K79me; robotic mouse model analysis Human molecular genetics High 17135274
2008 MLL-AF4 fusion promotes H3K79 methylation at target gene loci. Suppression of the H3K79 methyltransferase DOT1L inhibits expression of critical MLL-AF4 target genes, establishing a mechanistic link between MLL-AF4, DOT1L recruitment, and H3K79 methylation-dependent gene activation. ChIP-chip analysis of H3K79 methylation, DOT1L inhibition experiment, gene expression profiling Cancer cell High 18977325
2009 Af4 directly regulates transcription of the Igf-1 gene in Purkinje cells, as confirmed by chromatin immunoprecipitation. Loss/reduction of Igf-1 leads to decreased downstream IGF-1R and ERK1/2 activation, and IGF-1 treatment delayed Purkinje cell death in robotic mice. Laser capture microdissection followed by microarray, chromatin immunoprecipitation (ChIP), IGF-1 treatment of robotic mice, immunoblot for IGF-1R and ERK phosphorylation The Journal of neuroscience High 20007461
2010 Affinity purification of the AF4 protein complex identified 11 binding partners including P-TEFb kinase and demonstrated P-TEFb-mediated activation of promoter-arrested RNA Pol II, together with chromatin-modifying activities. The AF4-MLL fusion complex contains at least 16 constituents, additionally including H3K4(me3) and H3K79(me3) histone methyltransferases, a protein arginine N-methyltransferase, and a histone acetyltransferase, causing disturbed RNA Pol II activation and altered histone methylation signatures. Affinity purification, mass spectrometry, in vitro RNA Pol II transcription elongation assay Leukemia High 21030982
2012 AF4 directly promotes CD133 (PROM1) transcription. Knockdown of AF4 causes a dramatic reduction in CD133 transcript levels across multiple cancer cell lines, and CD133 is required for leukemia cell survival in MLL-AF4+ ALL cells. Large-scale RNAi screen, siRNA knockdown, RT-PCR/qPCR for CD133, cell viability assay Cancer research Medium 22337994
2013 AFF1 is a ubiquitous component of the P-TEFb network: it is bound to CDK9-CycT and present in all major P-TEFb complexes (7SK snRNP, SECs, and Brd4-P-TEFb complex). The tripartite CDK9-CycT-AFF1 complex is transferred as a unit within the network. AFF1 increases Tat's affinity for CycT1, facilitating Tat's extraction of P-TEFb from 7SK snRNP and formation of Tat-SECs for HIV transcription. Co-immunoprecipitation, affinity purification, in vitro P-TEFb extraction assay, HIV transactivation reporter assay Proceedings of the National Academy of Sciences of the United States of America High 24367103
2016 DDX6, a DEAD-box RNA helicase, binds to 7SK snRNA and transfers P-TEFb to the AF4/AF4N (AFF1) super elongation complex. DDX6 also stably binds AF4 and AF4N. Co-overexpression of AF4/AF4N with DDX6 causes an 11-fold increase in mRNA production, while DDX6 knockdown decreases mRNA production by 70%. GST pull-down, co-immunoprecipitation, mRNA production assay, siRNA knockdown American journal of blood research Medium 27679741
2017 AFF1 regulates expression of DKK1 by directly binding to its promoter region. Depletion of AFF1 in human MSCs increases osteogenic differentiation (ALP activity, mineralization, osteogenic gene expression), and knockdown of DKK1 in AFF1-overexpressing MSCs abrogates the impairment of osteogenic differentiation, placing AFF1 upstream of DKK1 in MSC osteogenesis. siRNA knockdown, ChIP for AFF1 at DKK1 promoter, ALP activity assay, mineralization assay, in vivo bone formation assay Bone research High 28955517
2019 p300 acetylates AFF1 at a specific site, reducing its interaction with other super elongation complex (SEC) components and impairing P-TEFb-mediated CTD phosphorylation of RNA Pol II both in vitro and in vivo. Upon genotoxic stress, p300-mediated AFF1 acetylation is dynamically induced and correlates with global transcriptional downregulation. Re-expression of wild-type AFF1, but not an acetylation-mimic mutant, restores SEC recruitment and target gene expression. In vitro acetylation assay, in vitro P-TEFb CTD kinase assay, co-immunoprecipitation, mutagenesis (acetylation-mimic mutant), ChIP, rescue expression experiment Proceedings of the National Academy of Sciences of the United States of America High 31611376
2021 MLL-ELL recruits an AF4/ENL/P-TEFb (AEP) complex—containing AFF1 (AF4)—to target promoters to activate transcription in murine hematopoietic progenitors. The C-terminal portion of ELL provides a binding platform for AF4 (as well as EAF1 and p53). The HBO1 complex promotes AEP (AFF1-containing SEC) association over EAF1. Co-immunoprecipitation, ChIP-seq, murine leukemia transformation assay, domain mapping eLife Medium 34431785
2022 Disruption of 7SK snRNP causes complete dissociation of the Cdk9/CycT1 heterodimer into monomers under stress conditions. AFF1-containing SEC (along with Brd4) then recruits monomerized Cdk9 and CycT1 on chromatin, reassembling active P-TEFb and inducing autophosphorylation of Cdk9 T186. Co-immunoprecipitation under stress conditions, Cdk9 T186 phosphorylation assay, chromatin fractionation Nucleic acids research Medium 34935961

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell 854 1423625
2008 H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer cell 438 18977325
1988 Monoclonal antibodies to the major feline allergen Fel d I. II. Single step affinity purification of Fel d I, N-terminal sequence analysis, and development of a sensitive two-site immunoassay to assess Fel d I exposure. Journal of immunology (Baltimore, Md. : 1950) 267 3276780
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 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 136 25084738
2010 The AF4.MLL fusion protein is capable of inducing ALL in mice without requirement of MLL.AF4. Blood 125 20194896
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
2009 Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene. The Journal of experimental medicine 103 19995953
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 103 10589005
1996 LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias. Blood 97 8555498
2006 A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy. Blood 95 16551973
2004 Fel d 4, a cat lipocalin allergen. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 92 15544598
2015 Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia. Blood 91 26463423
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
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
2006 A conditional model of MLL-AF4 B-cell tumourigenesis using invertor technology. Oncogene 80 16607274
2011 Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia. Blood 78 21389315
2009 The major cat allergen, Fel d 1, in diagnosis and therapy. International archives of allergy and immunology 76 19844127
1997 Exon/intron structure of the human AF-4 gene, a member of the AF-4/LAF-4/FMR-2 gene family coding for a nuclear protein with structural alterations in acute leukaemia. British journal of haematology 76 9233580
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
2001 Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation. Proceedings of the National Academy of Sciences of the United States of America 68 11493704
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 67 24367103
2010 The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia 67 21030982
2004 Interaction of AF4 wild-type and AF4.MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology? Oncogene 66 15221006
2010 A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells. Cell cycle (Georgetown, Tex.) 61 20237425
2017 Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia. The Journal of clinical investigation 59 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
2005 The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. Proceedings of the National Academy of Sciences of the United States of America 56 16169901
2022 Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia. Blood 54 35839448
2010 Insights into the cellular origin and etiology of the infant pro-B acute lymphoblastic leukemia with MLL-AF4 rearrangement. Leukemia 53 21135858
2013 The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial. Haematologica 49 23349309
2011 Two newly identified cat allergens: the von Ebner gland protein Fel d 7 and the latherin-like protein Fel d 8. International archives of allergy and immunology 47 21576986
2020 H3K79me2/3 controls enhancer-promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells. Leukemia 46 32242051
2014 Flavonoid-enriched apple fraction AF4 induces cell cycle arrest, DNA topoisomerase II inhibition, and apoptosis in human liver cancer HepG2 cells. Nutrition and cancer 45 25256427
2012 A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification. Cell research 45 22212479
2004 The synthetic peptide PFWT disrupts AF4-AF9 protein complexes and induces apoptosis in t(4;11) leukemia cells. Leukemia 45 15269783
2001 Lilliputian: an AF4/FMR2-related protein that controls cell identity and cell growth. Development (Cambridge, England) 44 11171403
2006 Combined effects of the two reciprocal t(4;11) fusion proteins MLL.AF4 and AF4.MLL confer resistance to apoptosis, cell cycling capacity and growth transformation. Oncogene 43 17130830
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
2012 The mixed lineage leukemia (MLL) fusion-associated gene AF4 promotes CD133 transcription. Cancer research 41 22337994
2021 The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis. Leukemia 39 34321607
2017 AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs. Bone research 39 28955517
2016 Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development. Cell reports 39 27396339
2002 Panhandle and reverse-panhandle PCR enable cloning of der(11) and der(other) genomic breakpoint junctions of MLL translocations and identify complex translocation of MLL, AF-4, and CDK6. Proceedings of the National Academy of Sciences of the United States of America 39 11930009
1993 Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia. Cancer research 39 8358709
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
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
1998 AF4 encodes a ubiquitous protein that in both native and MLL-AF4 fusion types localizes to subnuclear compartments. Blood 31 9808577
1998 Complement-inhibiting cucurbitacin glycosides from Picria fel-terrae. Journal of natural products 30 9644059
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
2021 miR-130b and miR-128a are essential lineage-specific codrivers of t(4;11) MLL-AF4 acute leukemia. Blood 27 34111240
2001 Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5' MLL sequences in chromosome 4. Leukemia 27 11368362
2017 The full transforming capacity of MLL-Af4 is interlinked with lymphoid lineage commitment. Blood 25 28637661
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
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 24 30728436
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
2021 HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis. eLife 23 34431785
2016 MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylation. Experimental hematology 23 27856324
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
2010 t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. Leukemia research 22 20869771
2001 Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein. Blood 22 11719380
2024 Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles. Journal of extracellular vesicles 21 39001700
2022 Evolutionary Biology and Gene Editing of Cat Allergen, Fel d 1. The CRISPR journal 21 35343817
2007 The AF4-mimetic peptide, PFWT, induces necrotic cell death in MV4-11 leukemia cells. Leukemia research 21 17875318
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
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
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
2011 Resistance of MLL-AFF1-positive acute lymphoblastic leukemia to tumor necrosis factor-alpha is mediated by S100A6 upregulation. Blood cancer journal 19 22829076
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
2009 Multistep pathogenesis of leukemia via the MLL-AF4 chimeric gene/Flt3 gene tyrosine kinase domain (TKD) mutation-related enhancement of S100A6 expression. Experimental hematology 18 19463771
2024 Targeting IGF2BP3 enhances antileukemic effects of menin-MLL inhibition in MLL-AF4 leukemia. Blood advances 17 38048400
2021 Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements. Cell reports 17 34706236
2016 Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair. Oncotarget 17 27119507
2012 Association of AFF1 rs340630 and AFF3 rs10865035 polymorphisms with systemic lupus erythematosus in a Chinese population. Immunogenetics 17 22983539
2006 Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited. BMC cancer 17 16433901
2022 Disrupting the Cdk9/Cyclin T1 heterodimer of 7SK snRNP for the Brd4 and AFF1/4 guided reconstitution of active P-TEFb. Nucleic acids research 16 34935961
2017 Amlexanox Downregulates S100A6 to Sensitize KMT2A/AFF1-Positive Acute Lymphoblastic Leukemia to TNFα Treatment. Cancer research 16 28646023
2020 HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia. Experimental hematology 15 33069783
2020 Structural Transformations and Spin-Crossover in [FeL2 ]2+ Salts (L=4-{tert-Butylsulfanyl}-2,6-di{pyrazol-1-yl}pyridine): The Influence of Bulky Ligand Substituents. Chemistry (Weinheim an der Bergstrasse, Germany) 15 33073890
2019 Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation between AF4-MLL and MLL-AF4 fusions. Haematologica 15 30679325
2018 Induction of bystander tolerance and immune deviation after Fel d 1 peptide immunotherapy. The Journal of allergy and clinical immunology 15 29906527
2016 Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review). Oncology reports 15 27431573
2010 Activation of Ras-dependent Elk-1 activity by MLL-AF4 family fusion oncoproteins. Experimental hematology 15 20362031
2007 Down-regulation of DLX3 expression in MLL-AF4 childhood lymphoblastic leukemias is mediated by promoter region hypermethylation. Oncology reports 15 17611665
2018 Another cat and mouse game: Deciphering the evolution of the SCGB superfamily and exploring the molecular similarity of major cat allergen Fel d 1 and mouse ABP using computational approaches. PloS one 14 29771985
2012 Regulation of AMP-activated protein kinase signaling by AFF4 protein, member of AF4 (ALL1-fused gene from chromosome 4) family of transcription factors, in hypothalamic neurons. The Journal of biological chemistry 14 22528490

Missed literature

Know a paper Affinage missed for AFF1? Flag it for the maintainers and the community.

No submissions yet.