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    BIOMARKER:

    BIRC3 mutation

    i
    Other names: BIRC3, API2, c-IAP2, cIAP2, hiap-1, MALT2, MIHC, RNF49, Baculoviral IAP repeat containing 3
    Entrez ID:
    330
    Related biomarkers:
    Expression
    CNA
    Fusion
    1year
    Novel Plasma Cell-Free RNA-Based Liquid Biopsy Approach for CLL (ASH 2024)
    Conclusions The presented liquid biopsy-based approach demonstrates the feasibility of identifying malignant cell fraction, BCR repertoires, clinically significant mutations, and immune and tissue specific processes from cfRNA. This study also suggests that the cfRNA platform may support longitudinal monitoring of CLL progression and relapse, as well the development of MRD tests with future validation.
    Liquid biopsy • Biopsy
    |
    TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • BIRC3 (Baculoviral IAP repeat containing 3)
    |
    TP53 mutation • ATM mutation • SF3B1 mutation • BIRC3 mutation
    |
    BostonGene Tumor Portrait™ Test
    2years
    DNA Methylation-Based Classification of Hairy Cell Leukemia and Splenic B Cell Lymphoma (ASH 2023)
    In summary, we have developed a DNA methylation-based classifier that resolves 4 SBLPN subgroups with distinct molecular features, and reclassifies a subset of SMZL and HCL patients, adding further information to the updated WHO/ICC entities. We reveal distinct biological pathways operating in M-SBLPN subgroups that may aid targeted therapy approaches.
    Epigenetic controller
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • TERT (Telomerase Reverse Transcriptase) • IGH (Immunoglobulin Heavy Locus) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • BIRC3 (Baculoviral IAP repeat containing 3) • IL2RA (Interleukin 2 receptor, alpha) • SYK (Spleen tyrosine kinase) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
    |
    TP53 mutation • BRAF V600E • BRAF V600 • BIRC3 mutation • TERT mutation • NOTCH2 mutation • TERT promoter mutation • SYK mutation • TERT 124C>T
    3years
    Potential Drivers of Acquired Resistance to Idelalisib in CLL Patients (ASH 2022)
    We checked the phosphorylation/activation level of AKT and ERK1/2 at the responding and progression time points in the three original CLL patients with acquired resistance and observed that pERK levels are inhibited by idelalisib at baseline, but not at progression, in 2 patients (patient 1 and 2). In conclusion, we have identified potential drivers of acquired resistance to idelalisib in CLL patients, including MAPK pathway activation as in our prior study, and we continue with ongoing work evaluating the potential role of PI3K pathway mutations, BIRC3, AICDA and LTK in treatment resistance, since insights from these studies will help us guide therapy for CLL patients with refractory disease.
    Clinical • Preclinical • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CD79B (CD79b Molecule) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BIRC3 (Baculoviral IAP repeat containing 3) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • IKZF3 (IKAROS Family Zinc Finger 3) • LTK (Leukocyte Receptor Tyrosine Kinase) • NFATC1 (Nuclear Factor Of Activated T Cells 1) • PDIA3 (Protein Disulfide Isomerase Family A Member 3) • DDX3X (DEAD-Box Helicase 3 X-Linked) • NFATC3 (Nuclear Factor Of Activated T Cells 3)
    |
    TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • ATM mutation • RAS mutation • SF3B1 mutation • BIRC3 mutation • PIK3R1 mutation
    |
    Zydelig (idelalisib)
    3years
    A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphoma (clinicaltrials.gov)
    P1, N=20, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • POT1 (Protection of telomeres 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    |
    CD20 positive • Chr t(11;14) • KMT2D mutation • BIRC3 mutation • CCND1 overexpression • SMARCA4 mutation • Chr t(11;14)(q13;q32) • MYC positive
    |
    Rituxan (rituximab) • cyclophosphamide • Calquence (acalabrutinib) • fludarabine IV • Tecartus (brexucabtagene autoleucel)
    3years
    Integrating Multi-Omics to Reveal the Clonal Evolutionary Characteristics in CLL Patients with Zanubrutinib Resistance (ASH 2022)
    Introduction The drug-resistant mechanisms of the first-generation Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been extensively explored in chronic lymphocytic leukemia (CLL) patients. Integrated multi-omics were performed in our zanubrutinib-resistant CLL patients cohort. Due to spatial heterogeneity and clonal evolution among patients, deep targeted-gene NGS and ddPCR should be used complementarily to evaluate the emergence of resistant clones. BTK Cys481 and Leu528 were two main BTK resistant mutations in zanubrutinib resistant CLL patients.
    Clinical • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • MCL1 (Myeloid cell leukemia 1) • BIRC3 (Baculoviral IAP repeat containing 3) • PAX5 (Paired Box 5) • PLCG2 (Phospholipase C Gamma 2) • IRF8 (Interferon Regulatory Factor 8) • FOXP1 (Forkhead Box P1) • KLF8 (Kruppel Like Factor 8) • ATF3 (Activating Transcription Factor 3) • IRF5 (Interferon Regulatory Factor 5)
    |
    TP53 mutation • BCL2 overexpression • SF3B1 mutation • BCL2 expression • BIRC3 mutation • MCL1 expression • PLCG2 mutation • BTK mutation
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
    3years
    Molecular Landscape of Chronic Lymphocytic Leukemia Using Targeted Gene Panel Sequencing (ASH 2022)
    FBXW7 and NOTCH1 pathogenic variants have the same biological consequences in CLL, therefore presence of FBXW7 mutations may have clinical relevance regarding anti-CD20 therapy. Taken together, these NGS results complemented with the study of IGHV mutational status and cytogenetic data can contribute to better prognostic workup and management of our CLL patients.
    IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SF3B1 (Splicing Factor 3b Subunit 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IGH (Immunoglobulin Heavy Locus) • CD79B (CD79b Molecule) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BIRC3 (Baculoviral IAP repeat containing 3) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CARD11 (Caspase Recruitment Domain Family Member 11) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • PLCG2 (Phospholipase C Gamma 2) • MAPK1 (Mitogen-activated protein kinase 1) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • TCF3 (Transcription Factor 3) • POT1 (Protection of telomeres 1) • DDX3X (DEAD-Box Helicase 3 X-Linked)
    |
    TP53 mutation • PIK3CA mutation • NOTCH1 mutation • Chr del(11q) • SF3B1 mutation • IGH mutation • BIRC3 mutation • FBXW7 mutation • TS 12
    3years
    Molecular determinants of outcomes in relapsed or refractory mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trial. (PubMed, Leukemia)
    Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers on routine patient samples that can meaningfully inform clinical practice.
    Journal
    |
    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1) • BIRC3 (Baculoviral IAP repeat containing 3)
    |
    MYC expression • BIRC3 mutation
    |
    Imbruvica (ibrutinib) • Torisel (temsirolimus)
    over3years
    A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphoma (clinicaltrials.gov)
    P1, N=20, Not yet recruiting, M.D. Anderson Cancer Center | N=50 --> 20
    Enrollment change
    |
    TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • POT1 (Protection of telomeres 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    |
    CD20 positive • Chr t(11;14) • KMT2D mutation • BIRC3 mutation • CCND1 overexpression • SMARCA4 mutation • Chr t(11;14)(q13;q32) • MYC positive
    |
    Rituxan (rituximab) • cyclophosphamide • Calquence (acalabrutinib) • fludarabine IV • Tecartus (brexucabtagene autoleucel)
    over3years
    The correlation of CD49d expression pattern with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    There were significant correlations between CD49d and 11q22-, +12 and BIRC3 gene mutation. Patients with bimodal CD49d were more correlated with poor prognosis indexes.
    Journal
    |
    BIRC3 (Baculoviral IAP repeat containing 3) • ITGA4 (Integrin, alpha 4)
    |
    BIRC3 mutation • ITGA4 negative
    over3years
    A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphoma (clinicaltrials.gov)
    P1, N=50, Not yet recruiting, M.D. Anderson Cancer Center
    New P1 trial
    |
    TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • POT1 (Protection of telomeres 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    |
    CD20 positive • Chr t(11;14) • KMT2D mutation • BIRC3 mutation • CCND1 overexpression • SMARCA4 mutation • Chr t(11;14)(q13;q32) • MYC positive
    |
    Rituxan (rituximab) • cyclophosphamide • Calquence (acalabrutinib) • fludarabine IV • Tecartus (brexucabtagene autoleucel)
    over3years
    VENETOCLAX IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA WITH 17P DELETION: 6-YEAR FOLLOW-UP AND GENOMIC ANALYSES IN A PIVOTAL PHASE 2 TRIAL (EHA 2022)
    Of pts with PD (n=98) or whose disease was refractory to Ven (n=11), 73 received another LOT, most commonly ibrutinib (n=41); mOS from ibrutinib initiation was 28.0 mo. Conclusion At end of study (median f/u, 70 mo), 48% of pts were alive, 24% were progression-free, and 16% remained on Ven, confirming the long-term activity of Ven in this high-risk population with del(17p) CLL and median 2 prior LOT. Except SF3B1 mutation, other adverse features (eg, >1 TP53 mutation, NOTCH1 mutations, unmutated IGHV) did not influence outcomes with Ven treatment in this cohort.
    P2 data • Clinical • IO biomarker
    |
    TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • IGH (Immunoglobulin Heavy Locus) • BIRC3 (Baculoviral IAP repeat containing 3)
    |
    TP53 mutation • ATM mutation • NOTCH1 mutation • SF3B1 mutation • TP53 mutation + Chr del(17p) • BIRC3 mutation
    |
    clonoSEQ
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib)