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    GENE:

    CREBBP (CREB binding protein)

    i
    Other names: CREBBP, CBP, KAT3A, RSTS, RTS, CREB binding protein
    5d
    Different primary thyroid B-cell lymphomas show overlapping mutation profiles, suggesting involvement of a common pathogenic process. (PubMed, Haematologica)
    In contrast, majority of BCL6 translocations in thyroid EMZL juxtaposed the BCL6 gene to the IGHJ/D region without encompassing the Eμ enhancer or its partner genes in an opposite orientation, thus less likely to lead to constitutive BCL6 transactivation. The above genetic changes likely dysregulate B-cell maturation and peripheral tolerance, thus offer significant molecular insights into the pathogenesis of thyroid lymphomas, particularly underpinning autoimmunity in the lymphomagenesis and potentially explaining the overlap in histopathology between EMZL and FL.
    Journal • IO biomarker
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    PD-L1 (Programmed death ligand 1) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • TNFRSF14 (TNF Receptor Superfamily Member 14) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
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    TET2 mutation • EZH2 mutation
    5d
    Impact of BRAF, TERT, and novel mutations on the efficacy of lenvatinib for advanced papillary thyroid cancer: A national genomic database analysis. (PubMed, NPJ Precis Oncol)
    Conclusions Lenvatinib showed substantial efficacy in BRAF-mutated PTC, while TERT mutations did not predict poor outcomes. The identification of five genes associated with early treatment failure highlights the potential for genomic biomarkers to guide personalized therapy.
    Journal
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    BRAF (B-raf proto-oncogene) • TERT (Telomerase Reverse Transcriptase) • mTOR (Mechanistic target of rapamycin kinase) • KMT2A (Lysine Methyltransferase 2A) • CREBBP (CREB binding protein) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • MUTYH (MutY homolog)
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    BRAF mutation • MLL mutation
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    Lenvima (lenvatinib)
    5d
    WDHD1 promotes hepatocellular carcinoma progression by affecting the cell cycle and immune evasion. (PubMed, Transl Oncol)
    Additionally, high WDHD1 levels were associated with increased CD4 memory T cell infiltration, elevated tumor mutational burden (TMB), and enhanced expression of key immune checkpoint markers, suggesting a potential for improved response to immunotherapy in these patients. These findings suggest WDHD1 as a novel oncogenic driver and promising therapeutic target in HCC.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • CREBBP (CREB binding protein) • CD4 (CD4 Molecule) • EP300 (E1A binding protein p300) • MIR139 (MicroRNA 139) • CDC45 (Cell Division Cycle 45) • MIR22 (MicroRNA 22)
    5d
    Inhibition of p300/CREBBP catalytic activity drives context-dependent transcriptional activation in AML. (PubMed, Blood)
    Therapeutically, combining KAT inhibition with interferon-alpha augmented ISG expression, synergistically drove AML cell death in vitro and significantly extended survival in both AML xenografts and murine models. These findings refine our understanding of p300/CREBBP KAT activity, demonstrating that cooperative TF assembly can reconfigure p300/CREBBP-containing complexes under catalytic inhibition to induce transcription, with translational implications for reprogramming interferon-driven programs through catalytic inhibition in AML and beyond.
    Journal
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    CREBBP (CREB binding protein) • STAT1 (Signal Transducer And Activator Of Transcription 1)
    16d
    Ocular adnexa follicular lymphoma: clinicopathological study of 23 patients. (PubMed, Virchows Arch)
    Most OA FLs followed an indolent course with good outcomes after local therapy, though transformation to diffuse large B-cell lymphoma occurred in a subset of two cases. Our results suggest that OA FL exhibits genetic heterogeneity, combining molecular features from both subtypes, and highlight the importance of thorough staging and individualised therapeutic and surveillance strategies for each patient.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • TNFRSF14 (TNF Receptor Superfamily Member 14) • FCER2 (Fc Fragment Of IgE Receptor II)
    20d
    HAP2HCT: TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies (clinicaltrials.gov)
    P2, N=69, Active, not recruiting, St. Jude Children's Research Hospital | N=140 --> 69 | Trial completion date: Aug 2025 --> Jun 2026
    Enrollment change • Trial completion date
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    FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • WT1 (WT1 Transcription Factor) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • HOXA9 (Homeobox A9) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • KAT6A (Lysine Acetyltransferase 6A) • KDM5A (Lysine Demethylase 5A) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
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    FLT3-ITD mutation
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    cyclophosphamide • Blincyto (blinatumomab) • melphalan • fludarabine IV • mesna • thiotepa • Neupogen (filgrastim)
    27d
    Differential role of CREBBP missense and truncating mutations in germinal center development and lymphomagenesis. (PubMed, Blood)
    Of note, lymphoma cells with CREBBPRH and CREBBP loss showed distinct sensitivity to CREBBP/p300 small molecule inhibitors. Together with the differential distribution of missense and truncating mutations in FL and DLBCL, these findings have implications for the pathogenesis and therapeutic targeting of these cancers.
    Journal
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    CREBBP (CREB binding protein)
    29d
    Overcoming Menin inhibitor resistance in AML cells with combinations including BET proteins and dual BRG1/BRM inhibitor. (PubMed, Blood)
    Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLL1-r AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1-r or mtNPM1.
    Journal
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    NPM1 (Nucleophosmin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CREBBP (CREB binding protein) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1) • BRD4 (Bromodomain Containing 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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    NPM1 mutation • MLL rearrangement • MLL mutation
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    Revuforj (revumenib) • birabresib (OTX015) • camibirstat (FHD-286)
    1m
    D8620C00001: A trial to learn how safe AZD3632 is, how well it works, and how it moves throughout the body over time in adults with acute leukemia and myelodysplastic syndrome with HOX gene overexpression (2025-521299-76-00)
    P1/2, N=17, Recruiting, AstraZeneca AB
    New P1/2 trial
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    NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NUP214 (Nucleoporin 214) • CDX2 (Caudal Type Homeobox 2)
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    NPM1 mutation • MLL mutation
    1m
    OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway. (PubMed, bioRxiv)
    Because PDE3B catalyzes the conversion of cAMP to AMP and thereby negatively regulating the cAMP-dependent PKA/CREB/CREBBP tumor suppressive pathway, the loss of OSTM1 leads to PDE3B stabilization and enhanced cell transformation. Our findings establish OSTM1 as a pivotal E3 ligase that prevents B-cell lymphomagenesis through the regulation of the cAMP/PKA/CREB pathway.
    Journal
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CREBBP (CREB binding protein)
    1m
    BAF complex-independent gene activation by SS18::SSX. (PubMed, bioRxiv)
    Our work reveals new therapeutic vulnerabilities in synovial sarcoma and suggests broader relevance for targeting coactivator-dependent transcription in fusion-driven cancers. BAF degradation does not alter SS18::SSX-activated transcriptional programsDirect SS18::SSX transcriptional activation is independent of BAF interactionThe SS18 C-terminus engages the co-activator EP300 to promote gene expressionSmall molecule degraders of EP300/CREBBP abolish SS18::SSX-mediated transcription.
    Journal
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    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)