News - CD58 mutation - LARVOL VERI

3ms

Specific Mutation Predict Relapse/Refractory Diffuse Large B-Cell Lymphoma. (PubMed, J Blood Med)

The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL)...In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients. Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.

3 months ago

Journal • IO biomarker

TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CARD11 (Caspase Recruitment Domain Family Member 11) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • CD58 (CD58 Molecule) • EBF1 (EBF Transcription Factor 1) • TBL1XR1 (TBL1X Receptor 1)

TP53 mutation • CARD11 mutation • CD58 mutation

Rituxan (rituximab)

8ms

CD58 alterations govern antitumor immune responses by inducing PD-L1 and IDO in diffuse large B-cell lymphoma. (PubMed, Cancer Res)

Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free and overall survival...Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PD-L1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to CAR T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL.

8 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD22 (CD22 Molecule) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • CD58 (CD58 Molecule) • CD2 (CD2 Molecule)

PD-L1 expression • IDO1 expression • CD58 expression • CD58 mutation

Rituxan (rituximab)

1year

Genetic Characterization of Primary Mediastinal B-Cell Lymphoma: Pathogenesis and Patient Outcomes. (PubMed, J Clin Oncol)

This large-scale genomic characterization of PMBCL identified novel treatment targets and genetic lesions for refined risk stratification. DUSP2 and CD58 mutation analyses may guide treatment decisions between rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.

1 year ago

Journal

ARID1A (AT-rich interaction domain 1A) • P2RY8 (P2Y Receptor Family Member 8) • CD58 (CD58 Molecule) • TP63 (Tumor protein 63) • DOCK8 (Dedicator Of Cytokinesis 8) • TP73 (Tumor Protein P73) • WWOX (WW Domain Containing Oxidoreductase)

CD58 mutation

Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine

1year

CD58 Genetic Alterations and Its Contribution to Upregulation of PD-L1 and IDO Via LYN/CD22/SHP1 Axis in DLBCL (ASH 2023)

Patients with CD58 mutation, copy number loss or low expression exhibited lower complete response rates following first-line R-CHOP therapy, as well as significantly poorer PFS and OS... Our study comprehensively characterized CD58 genetic alterations in DLBCL. We demonstrated that CD58 downregulation or mutation led to upregulation of PD-L1 and IDO expression mainly by regulating the LYN/CD22/SHP1 axis. Moreover, we explored strategies to directly activate CD2 co-stimulatory signaling or in combination with immune checkpoint inhibitors to address the diverse effects of CD58 alterations.

1 year ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • JAK2 (Janus kinase 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • CD22 (CD22 Molecule) • CD4 (CD4 Molecule) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • CD58 (CD58 Molecule) • CD2 (CD2 Molecule)

PD-L1 expression • MYD88 mutation • KMT2D mutation • CD79B mutation • IDO1 expression • CD58 mutation

Rituxan (rituximab)

1year

Multi-Dimensional Molecular and Tumor-Microenvironment Analysis of Classic Hodgkin Lymphoma (ASH 2023)

Conclusion Our multi-dimensional profiling approach enabled us to delineate molecular profiles of HRS cells that are linked to distinct TME patterns. These linkages have implications for current pathogenesis models, molecular subtyping of CHL, and identification of cellular vulnerabilities that might be therapeutically exploitable via targeting of HRS cell phenotypes and/or immune escape mechanisms.

1 year ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • B2M (Beta-2-microglobulin) • PD-L2 (Programmed Cell Death 1 Ligand 2) • CD4 (CD4 Molecule) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • BCL7A (BAF Chromatin Remodeling Complex Subunit BCL7A) • CD68 (CD68 Molecule) • SOCS1 (Suppressor Of Cytokine Signaling 1) • CD58 (CD58 Molecule) • FOXP3 (Forkhead Box P3) • STAT6 (Signal transducer and activator of transcription 6) • ZNF217 (Zinc Finger Protein 217) • H1-4 (H1.4 Linker Histone, Cluster Member) • TBL1XR1 (TBL1X Receptor 1)

TNFRSF8 expression • B2M mutation • MHC-II expression • CD58 mutation • SPEN mutation

2years

PAX5 epigenetically orchestrates CD58 transcription and modulates blinatumomab response in acute lymphoblastic leukemia. (PubMed, Sci Adv)

We described a PAX5-driven enhancer at the CD58 locus, which was disrupted by PAX5 P80R, and the loss of CD58 abolished blinatumomab-induced T cell activation with global changes in transcriptomic/epigenomic program. In conclusion, we identified previously unidentified genetic mechanisms of blinatumomab resistance in B-ALL, suggesting strategies for genomics-guided treatment individualization.

2 years ago

Journal • IO biomarker

CD19 (CD19 Molecule) • PAX5 (Paired Box 5) • CD58 (CD58 Molecule)

CD58 mutation

Blincyto (blinatumomab)

2years

Comprehensive Analysis of TP53 and CD58 Mutations and Identification of Patients with Inferior Prognosis and Enhanced Immune Escape in Diffuse Large B Cell Lymphoma (ASH 2022)

Our findings suggest that TP53 mutation alone is insufficient to effectively differentiate the risk of DLBCL. The mutually exclusive patterns between TP53 and CD58 mutations accurately stratified patients with DLBCL to permit the optional immunotherapy.

2 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

TP53 (Tumor protein P53) • IL6 (Interleukin 6) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD58 (CD58 Molecule) • DDX3X (DEAD-Box Helicase 3 X-Linked)

TP53 mutation • TP53 wild-type • TP53 expression • CD58 mutation

over2years

GENETIC AND EPIGENETIC FACTORS DRIVING PRIMARY MEDIASTINAL B-CELL LYMPHOMA PATHOGENESIS AND OUTCOME (EHA 2022)

Notably, DUSP2 mutated patients (25%) showed a similar outcome for CR rate, PFS and OS when comparing CHOP-like and intensified treatment regimens, suggesting no further benefit from treatment intensification in this very-low risk patient population. Conclusion Here, we present the genetic landscape of PMBCL highlighting a previously underappreciated role of chromatin modifying genes, identify novel treatment targets and provide a solid basis for guiding precision medicine approaches.

over 2 years ago

Tumor Mutational Burden

TMB (Tumor Mutational Burden) • B2M (Beta-2-microglobulin) • PAX5 (Paired Box 5) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • SOCS1 (Suppressor Of Cytokine Signaling 1) • CD58 (CD58 Molecule) • STAT6 (Signal transducer and activator of transcription 6) • ZNF217 (Zinc Finger Protein 217) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5) • NFKBIE (NFKB Inhibitor Epsilon) • TP73 (Tumor Protein P73)

CD58 mutation

3years

Detection of Aberrant CD58 Expression in a Wide Spectrum of Hodgkin and Non-Hodgkin Lymphomas: Implications for CAR T Cell Resistance (USCAP 2022)

We show that CD58 is lost in a significant proportion of all subtypes of lymphomas. As eligibility for CAR T therapy is being extended to a broader spectrum of lymphomas, mechanisms of resistance, such as CD58 loss, may limit therapeutic success. CD58 status is therefore an important biomarker in lymphoma patients who may benefit from next generation CARs with increased efficacy and other novel approaches that mitigate immune escape.

3 years ago

CAR T-Cell Therapy

CD19 (CD19 Molecule) • CD58 (CD58 Molecule) • CD2 (CD2 Molecule)

CD58 mutation

3years

Comprehensive Analysis of TP53 Mutation Characteristics and Identification of Patients with Inferior Prognosis and Enhanced Immune Escape in Diffuse Large B Cell Lymphoma (ASH 2021)

These patients with TP53WT&CD58MUT mutation pattern represent the candidate populations for immune therapy. Conclusions : Our findings indicated that the mutation patterns of TP53 and CD58 accurately stratified patients with DLBCL to permit the optional immunotherapy.

3 years ago

Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD58 (CD58 Molecule) • TDO2 (Tryptophan 2,3-Dioxygenase)

TP53 mutation • CD58 mutation

over3years

[VIRTUAL] Adult T-Cell Lymphoma/Leukemia With T-Helper Follicular (Tfh) Immunophenotypic Features (CAP 2021)

Here, expression of BCL6 and PD-1 raises a concern for T-cell neoplasm with Tfh origin, but was excluded on the basis of HTLV-1 PCR and supported by molecular genetic studies. This case highlights the immunophenotypic spectrum of ATLL, which can be a potential diagnostic pitfall.

over 3 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • BCL6 (B-cell CLL/lymphoma 6) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • CCND3 (Cyclin D3) • MME (Membrane Metalloendopeptidase) • CD58 (CD58 Molecule) • CD7 (CD7 Molecule) • ETS1 (ETS Proto-Oncogene 1) • PRDM1 (PR/SET Domain 1) • CD2 (CD2 Molecule)

TP53 mutation • PD-1 expression • CD58 mutation

over3years

Prognostic and therapeutic value of somatic mutations in diffuse large B-cell lymphoma: A systematic review. (PubMed, Crit Rev Oncol Hematol)

On the other hand, different approaches regarding targeted therapy have been proposed. Therefore, mutational analysis could help guide treatment choice in DLBCL yet further studies and clinical trials are needed.

over 3 years ago

Review • Journal

TP53 (Tumor protein P53) • CD58 (CD58 Molecule)

TP53 mutation • CD58 mutation