^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    GENE:

    KLHL6 (Kelch Like Family Member 6)

    i
    Other names: KLHL6, Kelch Like Family Member 6, Kelch-Like Protein 6, Kelch-Like 6 (Drosophila), Kelch-Like Protein KLHL6
    1m
    The ubiquitin ligase KLHL6 drives resistance to CD8+ T cell dysfunction. (PubMed, Nature)
    Enforcing KLHL6 expression in T cells markedly improved efficacy and long-term persistence against tumours and during viral infections in vivo. These findings uncover KLHL6 as a multifunctional, clinically actionable target for cancer immunotherapy, and highlight the potential of modulating proteostasis and ubiquitin modification to improve immunotherapy.
    Journal • IO biomarker
    |
    KLHL6 (Kelch Like Family Member 6)
    7ms
    Plasmablastic plasmacytoma followed by a plasmacytic plasma cell myeloma: insights into discordant extramedullary transformation-a case report and literature review. (PubMed, J Hematop)
    This case highlights the diagnostic complexity of plasmablastic plasmacytoma presenting as the initial manifestation of plasma cell myeloma. It underscores the necessity of a thorough evaluation, including bone marrow biopsy, to accurately differentiate plasmablastic transformation from PBL and ensure accurate diagnosis and appropriate management.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BMP6 (Bone Morphogenetic Protein 6) • KLHL6 (Kelch Like Family Member 6)
    |
    KRAS mutation
    over1year
    Tuning Responses to Polatuzumab Vedotin in B-cell Lymphoma. (PubMed, Cancer Discov)
    See related article by Corcoran et al., p. 1653 (6) See related article by Meriranta et al. (7).
    Journal
    |
    CD79B (CD79b Molecule) • KLHL6 (Kelch Like Family Member 6)
    |
    Polivy (polatuzumab vedotin-piiq)
    over1year
    Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology. (PubMed, Cancer Pathog Ther)
    The International Staging System (ISS) Stage III correlated with gene mutations in the NK-κB pathway while Revised ISS (R-ISS) Stage III correlated with the DNA damage repair pathway. There are various gene mutations in NDMM patients, mainly RAS/MAPK and NF-κB pathway gene pathways.
    Journal • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CCND1 (Cyclin D1) • SP140 (SP140 Nuclear Body Protein) • SDC1 (Syndecan 1) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • KLHL6 (Kelch Like Family Member 6) • EGR1 (Early Growth Response 1)
    over1year
    Transformation of t(14;18)-negative follicular lymphoma to plasmablastic lymphoma: a case report with analysis of genetic evolution. (PubMed, Diagn Pathol)
    We propose that transformation or divergent clonal evolution of FL into PBL can occur when relevant genetic mutations are present. This study broadens the spectrum of histological transformation of t(14;18)-negative FL and emphasizes its biological and clinical heterogeneity.
    Journal • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6) • CD38 (CD38 Molecule) • CD79B (CD79b Molecule) • CREBBP (CREB binding protein) • SDC1 (Syndecan 1) • TNFRSF14 (TNF Receptor Superfamily Member 14) • CD79A (CD79a Molecule) • IRF4 (Interferon regulatory factor 4) • MME (Membrane Metalloendopeptidase) • STAT6 (Signal transducer and activator of transcription 6) • KLHL6 (Kelch Like Family Member 6) • FCER2 (Fc Fragment Of IgE Receptor II)
    |
    Rituxan (rituximab) • bendamustine
    almost2years
    Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B Cell Lymphoma. (PubMed, Cancer Discov)
    We reveal how KLHL6 targets CD79B for degradation in normal and malignant germinal center B cells, thereby determining expression of the surface BCR complex. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic.
    Journal
    |
    CD79B (CD79b Molecule) • KLHL6 (Kelch Like Family Member 6)
    |
    Polivy (polatuzumab vedotin-piiq)
    almost2years
    Disruption of KLHL6 Fuels Oncogenic Antigen Receptor Signaling in B-cell Lymphoma. (PubMed, Blood Cancer Discov)
    Malfunctions of KLHL6 mutants extended beyond proximal BCR signaling with distinct phenotypes from KLHL6 silencing. Collectively, our findings uncover how recurrent mutations in KLHL6 alter BCR signaling and induce actionable phenotypic characteristics in DLBCL.
    Journal
    |
    CD79B (CD79b Molecule) • CD79A (CD79a Molecule) • KLHL6 (Kelch Like Family Member 6)
    |
    KLHL6 expression
    2years
    Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling. (PubMed, Front Oncol)
    Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • RAD21 (RAD21 Cohesin Complex Component) • KLHL6 (Kelch Like Family Member 6)
    |
    TP53 mutation • PIK3CA mutation • HER-2 mutation • FGFR1 mutation
    |
    FoundationOne® CDx
    2years
    Chronic Lymphocytic Leukemia IGHV Somatic Hypermutation Detection by Targeted Capture Next-Generation Sequencing. (PubMed, Clin Chem)
    A targeted capture approach to IGHV SHM detection can be integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.
    Journal • Next-generation sequencing • IO biomarker
    |
    TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SF3B1 (Splicing Factor 3b Subunit 1) • IGH (Immunoglobulin Heavy Locus) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • POT1 (Protection of telomeres 1) • KLHL6 (Kelch Like Family Member 6) • CHD2 (Chromodomain Helicase DNA Binding Protein 2)
    |
    IGH mutation
    over2years
    A Prospective Multicenter Phase II Study of Orelabrutinib-Lenalidomide-Rituximab (OLR) in Patients with Untreated Mantle Cell Lymphoma (MCL) in China (POLARIS Study): Preliminary Analysis on Efficacy, Safety, Mutation Spectrum and Impact of Mutation Profiling on Treatment Responses (ASH 2023)
    The preliminary findings show that the OLR exerted synergistic antitumor activity, with manageable toxicity in untreated MCL. Detection of PB ctDNA by NGS method may help to predict prognosis.
    Clinical • P2 data
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK12 (Cyclin dependent kinase 12) • BCOR (BCL6 Corepressor) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CARD11 (Caspase Recruitment Domain Family Member 11) • ARID2 (AT-Rich Interaction Domain 2) • GRIN2A (Glutamate Ionotropic Receptor NMDA Type Subunit 2A) • KDM5A (Lysine Demethylase 5A) • KLHL6 (Kelch Like Family Member 6) • MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14) • NFKBIE (NFKB Inhibitor Epsilon) • FANCC (FA Complementation Group C)
    |
    TP53 mutation • ATM mutation
    |
    Rituxan (rituximab) • lenalidomide • Inokai (orelabrutinib)
    over2years
    Resistance Mechanisms Impacting Bispecific Antibody (BsAbs) and Chimeric Antigen Receptor (CAR) T-Cell Therapy Outcomes in Large B Cell Lymphoma (LBCL) Patients (ASH 2023)
    In our study, a pattern of genetic alterations predicting worse OS was observed in patients treated with CAR T-cells (KLHL6, EP300 and MYC) and BsAbs (TP53, RHOA, PDL1, PDL2, GNAI2). This important information will aid in the development of targeted strategies to overcome resistance and improve treatment outcomes.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • PD-L2 (Programmed Cell Death 1 Ligand 2) • EP300 (E1A binding protein p300) • RHOA (Ras homolog family member A) • TNFRSF14 (TNF Receptor Superfamily Member 14) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5) • KLHL6 (Kelch Like Family Member 6)
    |
    TP53 mutation