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    BIOMARKER:

    PIM1 mutation

    i
    Other names: PIM1, Pim-1 Proto-Oncogene, Serine/Threonine Kinase, Serine/Threonine-Protein Kinase Pim-1, Proto-Oncogene Serine/Threonine-Protein Kinase Pim-1, Pim-1 Oncogene (Proviral Integration Site 1), Pim-1 Kinase 44 KDa Isoform, Pim-1 Oncogene, Oncogene PIM1, PIM
    Entrez ID:
    5292
    Related biomarkers:
    Expression
    17d
    Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Previously Untreated Diffuse Large B-Cell Lymphoma: A Real-World, Multi-Center, Retrospective Cohort Study. (PubMed, Hematol Oncol)
    While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.
    Retrospective data • Journal • Real-world evidence • IO biomarker • Real-world
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • PIM1 (Pim-1 Proto-Oncogene) • SOCS1 (Suppressor Of Cytokine Signaling 1)
    |
    TP53 mutation • PIM1 mutation
    |
    Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • prednisone • Polivy (polatuzumab vedotin-piiq)
    1m
    High-grade B-cell lymphoma not otherwise specified, with diffuse large B-cell lymphoma gene expression signatures: Genomic analysis and potential therapeutics. (PubMed, Am J Hematol)
    Frequent oncogenic PIM1 mutations were present in adult HGBCL, NOS. In vitro analyses with pharmacologic or genetic inhibition of PIM1 expression triggered B-cell activation and NF-κB-induced apoptosis, suggesting that PIM1 is a rational therapeutic target.
    Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • CARD11 (Caspase Recruitment Domain Family Member 11) • GNA13 (G Protein Subunit Alpha 13) • PIM1 (Pim-1 Proto-Oncogene) • CCND3 (Cyclin D3) • PRDM1 (PR/SET Domain 1) • DDX3X (DEAD-Box Helicase 3 X-Linked)
    |
    PIM1 mutation
    2ms
    Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.
    Retrospective data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2) • TBL1XR1 (TBL1X Receptor 1)
    |
    HER-2 mutation • PIM1 mutation
    |
    methotrexate IV
    10ms
    Mutational, immune microenvironment, and clinicopathological profiles of diffuse large B-cell lymphoma and follicular lymphoma with BCL6 rearrangement. (PubMed, Virchows Arch)
    In conclusion, both BCL6-R-positive FL and BCL6-R-positive DLBCL had a common mutational profile; but also, differences. DLBCL cases had a higher density of microenvironment markers.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • CD163 (CD163 Molecule) • ARID1B (AT-Rich Interaction Domain 1B) • CD36 (thrombospondin receptor) • IL10 (Interleukin 10) • RHOA (Ras homolog family member A) • PIM1 (Pim-1 Proto-Oncogene) • CSF1R (Colony stimulating factor 1 receptor) • HLA-B (Major Histocompatibility Complex, Class I, B) • H1-4 (H1.4 Linker Histone, Cluster Member) • PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) • BTG2 (BTG Anti-Proliferation Factor 2) • LAIR1 (Leukocyte Associated Immunoglobulin Like Receptor 1)
    |
    ATM mutation • MYD88 L265P • BCL6 rearrangement • ARID1B mutation • IL10-L • PIM1 mutation • MYC negative
    11ms
    The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis. (PubMed, Medicine (Baltimore))
    The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PIM1 (Pim-1 Proto-Oncogene)
    |
    MYD88 mutation • PIM1 mutation
    12ms
    Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy. (PubMed, World J Clin Oncol)
    Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.
    Clinical data • Journal • Combination therapy
    |
    PIM1 (Pim-1 Proto-Oncogene)
    |
    PIM1 mutation
    |
    Brukinsa (zanubrutinib) • methotrexate • methotrexate IV
    1year
    RCHOP Plus High-Dose Methotrexate As First-Line Therapy in Large B-Cell Lymphoma with Testis Involvement (ASH 2023)
    PTL may benefit from HD-MTX in preventing relapse, while alternative treatments should be explored for DLBCL-T. Future studies should consider PTL and DLBCL-T as separate entities to better understand their characteristics and optimize treatment strategies.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PD-1 (Programmed cell death 1) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • CARD11 (Caspase Recruitment Domain Family Member 11) • EP300 (E1A binding protein p300) • TCF3 (Transcription Factor 3) • PIM1 (Pim-1 Proto-Oncogene) • IRF4 (Interferon regulatory factor 4) • CD58 (CD58 Molecule) • PRDM1 (PR/SET Domain 1) • NFKBIE (NFKB Inhibitor Epsilon)
    |
    PD-L1 expression • MYD88 mutation • MYD88 L265P • PD-1 expression • BCL2 expression • MYC expression • CD79B mutation • PIM1 mutation
    |
    Rituxan (rituximab) • methotrexate IV
    1year
    The genetic landscape of histologically transformed marginal zone lymphomas. (PubMed, Cancer)
    The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • CARD11 (Caspase Recruitment Domain Family Member 11) • PIM1 (Pim-1 Proto-Oncogene) • CCND3 (Cyclin D3) • IRF4 (Interferon regulatory factor 4) • ID3 (Inhibitor Of DNA Binding 3, HLH Protein) • TBL1XR1 (TBL1X Receptor 1)
    |
    MYC expression • MYC rearrangement • BCL6 rearrangement • PIM1 mutation
    1year
    High-Dose Methotrexate, Ibrutinib and Temozolomide (MIT) for the Treatment of Newly Diagnosed Primary Central Nervous System Lymphoma: A Multi-Center Prospective Phase II Study (ASH 2023)
    The novel induction treatment of MIT achieved encouraging responses in newly diagnosed PCNSL patients with acceptable toxicities. The early clearance of ctDNA in CSF may be related to favorable survival.
    Clinical • P2 data
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2)
    |
    MYD88 mutation • PIM1 mutation
    |
    Imbruvica (ibrutinib) • temozolomide • methotrexate IV
    1year
    PIM1 Point Mutations Increase Migration of Diffuse Large B-Cell Lymphoma (DLBCL) Cells (ASH 2023)
    PIM1 mutations did not affect the proliferation of DLBCL cells and did not increase resistance to doxorubicin, excluding the proliferation rate or treatment resistance as a cause of the poor prognosis associated with PIM1 mutations...Finally, in transwell assays, PIM1 mutant cells exhibited markedly increased migratory potential. Taken together, these studies indicate that PIM1 mutants are not likely associated with differential drug responses, but rather facilitate tumor dissemination and are thus associated with inferior prognosis in DLBCL patients harboring PIM1 mutations.
    Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IFNG (Interferon, gamma) • CD79B (CD79b Molecule) • STAT3 (Signal Transducer And Activator Of Transcription 3) • PIM1 (Pim-1 Proto-Oncogene) • IL15 (Interleukin 15)
    |
    MYD88 mutation • MYD88 L265P • CD79B mutation • CD79B mutation • PIM1 mutation • MYD88 mutation + CD79B mutation
    |
    doxorubicin hydrochloride
    1year
    Landscape of BCL11B mutations in Human Cancer (AMP 2023)
    Our report represents one of the most extensive and detailed studies regarding the landscape of BCL11B point and indel mutations in human cancer. BCL11B alterations occur widely in mature, immature, B-cell, Tcell, and sarcomatous malignancies. TP53, PIM1, and SOCS1 are the most commonly co-mutated genes.
    TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PIM1 (Pim-1 Proto-Oncogene) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • SOCS1 (Suppressor Of Cytokine Signaling 1) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    PIM1 mutation • BCL11B mutation
    |
    FoundationOne® Heme CDx
    over1year
    Leukemic Presentation and Progressive Genomic Alterations of MCD/C5 Diffuse Large B-cell Lymphoma (DLBCL). (PubMed, Cold Spring Harb Mol Case Stud)
    Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Finally, the relapsed lymphoma cells showed in vitro resistance to standard BTK inhibitors but sensitivity to vecabrutinib, active against mutated BTK, and to PIM1 inhibitor. In summary, we provide in-depth molecular characterization of a case representing leukemic form of DLBCL and discuss mechanisms that may have contributed to lymphoma progression and development of drug resistance.
    Journal
    |
    TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • PRDM1 (PR/SET Domain 1) • TBL1XR1 (TBL1X Receptor 1)
    |
    TP53 mutation • CD79B mutation • PIM1 mutation
    |
    Imbruvica (ibrutinib) • Rituxan (rituximab) • bendamustine • vecabrutinib (SNS-062)
    over1year
    Molecular classification of systemic diffuse large B-cell lymphoma in Korea (ECP 2023)
    The identification of specific mutations in each subgroup, which were largely consistent with previous studies, indicates that the LymphGen classifier may be valuable in individualized treatment approaches for DLBCL patients. Additionally, this study demonstrates that unclassified group ("Other") may potentially be established as a distinct subgroup.
    IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • KMT2C (Lysine Methyltransferase 2C) • PIM1 (Pim-1 Proto-Oncogene) • IRF4 (Interferon regulatory factor 4) • SOCS1 (Suppressor Of Cytokine Signaling 1) • PRDM1 (PR/SET Domain 1) • BTG1 (BTG Anti-Proliferation Factor 1) • H1-4 (H1.4 Linker Histone, Cluster Member)
    |
    TP53 mutation • TET2 mutation • KMT2D mutation • EZH2 mutation • CD79B mutation • PIM1 mutation • BTG1 mutation • IRF4 mutation
    over1year
    IgH 3'RR recombination uncovers a non-germinal center imprint and c-MYC-dependent IgH rearrangement in unmutated chronic lymphocytic leukemia. (PubMed, Haematologica)
    In addition to the proposals already made concerning the CLL cell of origin, our study highlights that analysis of IGH recombinatory activity can identify CLL cases from different origins. Finally, on-going Sμ-3'RRrec in Sμ-3'RRrecHigh cells appeared to presumably be the consequence of high c-MYC expression, as c-MYC overexpression potentiated IGH rearrangements and Sμ-3'RRrec, even in the absence of AID for the latter.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • IGH (Immunoglobulin Heavy Locus) • PIM1 (Pim-1 Proto-Oncogene)
    |
    MYC overexpression • IGH mutation • MYC expression • MYC rearrangement • PIM1 mutation
    over1year
    CBF-beta mitigates PI3K-alpha-specific inhibitor killing through PIM1 in PIK3CA mutant gastric cancer. (PubMed, Mol Cancer Res)
    In this study we identified modulators of the response to the PI3K-alpha-specific inhibitor, BYL719, in PIK3CA mutant GCs...Our data provide clear mechanistic insights into PI3K-alpha inhibitor response in PIK3CA mutant gastric tumors and can inform future work as mutant selective inhibitors are in development for diverse tumor types. Implications: Loss of either NEDD9 or BCL-XL confers hyper-sensitivity to PI3K-alpha inhibition while loss of CBFB confers resistance through a CBFB/PIM1 signaling axis.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2L1 (BCL2-like 1) • PIM1 (Pim-1 Proto-Oncogene) • CBFB (Core-Binding Factor Subunit Beta 2)
    |
    PIK3CA mutation • PIM1 mutation
    |
    Piqray (alpelisib)
    over1year
    Activation-induced cytidine deaminase displays an alternative co-factor for modulating PIM1 expression in diffuse large B cell lymphoma cell lines. (PubMed, Cell Mol Biol (Noisy-le-grand))
    Our findings demonstrate that AID interacts with either DNMT1 or TET2 to form a complex to bind with a PIM1 promoter and thus is responsible for the modulation of PIM1 expression. These results provide insights into an alternative role of AID to DLBCL-associated genes.
    Preclinical • Journal
    |
    TET2 (Tet Methylcytosine Dioxygenase 2) • DNMT1 (DNA methyltransferase 1) • PIM1 (Pim-1 Proto-Oncogene)
    |
    PIM1 mutation
    over1year
    Real-World Data Analysis of Survival Outcomes and Central Nervous System Relapses in Testicular Diffuse Large B Cell Lymphoma. (PubMed, Cancer Manag Res)
    In our study, treatment with orchiectomy, six cycles of immunochemotherapy, and contralateral RT was effective. However, because CNS prophylaxis is an essential part of testicular DLBCL management, better treatment strategies than intrathecal therapy are required.
    Journal • Real-world evidence • Real-world
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene)
    |
    CD79B mutation • PIM1 mutation
    over1year
    MYD88 and MYD88 variants show different molecular characteristics and prognostic significance in diffuse large B-cell lymphoma. (PubMed, J Cancer Res Clin Oncol)
    The findings of this study indicate that DLBCL patients with MYD88 and MYD88 are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88 is not superior than those with MYD88, even poorer when focusing on the non-GCB subtype.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • PIM1 (Pim-1 Proto-Oncogene) • MME (Membrane Metalloendopeptidase)
    |
    LDH elevation • PIM1 mutation
    |
    Rituxan (rituximab)
    over1year
    Molecular heterogeneity of BCL2/MYC double expressor lymphoma underlies sensitivity to histone deacetylase inhibitor (ICML 2023)
    In conclusion, we identified three molecular subtypes of DEL, unveiled distinct genetic, transcriptional, and microenvironmental properties, and highlighted epigenetic therapeutic approaches for targeting histone acetylation in DEL.
    IO biomarker • Epigenetic controller
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene)
    |
    BCL2 overexpression • KMT2D mutation • MYC expression • CD79B mutation • CD79B mutation • PIM1 mutation
    |
    doxorubicin hydrochloride • Epidaza (chidamide)
    over1year
    Genomic landscape of follicular lymphoma across a wide spectrum of clinical behaviors. (PubMed, Hematol Oncol)
    Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • CREBBP (CREB binding protein) • PLCG2 (Phospholipase C Gamma 2) • EP300 (E1A binding protein p300) • IRF8 (Interferon Regulatory Factor 8) • PIM1 (Pim-1 Proto-Oncogene) • TNFRSF14 (TNF Receptor Superfamily Member 14) • TNFRSF18 (TNF Receptor Superfamily Member 18)
    |
    PIM1 mutation
    over1year
    Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.
    Retrospective data • Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2)
    |
    MYD88 mutation • PIM1 mutation
    almost2years
    The outcome of ibrutinib-based regimens in relapsed/refractory central nervous system lymphoma and the potential impact of genomic variants. (PubMed, Adv Clin Exp Med)
    Our study demonstrates that ibrutinib-based therapy is effective and relatively safe for the treatment of r/r CNSL. Patients with less genomic complexity, especially with regard to TMB, might benefit more from ibrutinib regimens.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene)
    |
    TMB-H • TMB-L • PIM1 mutation
    |
    Imbruvica (ibrutinib)
    almost2years
    Clinical features and prognosis of 166 cases of MYC/BCL2 double-expression diffuse large B-cell lymphoma (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    In patients with DEL, the overall response rate of R-EPOCH regimen was higher than that of RCHOP or RCHOP-like regimen (81.5% vs 63.4%, P=0.004) . DEL is a group of aggressive lymphomas with relatively poor PFS. The R-EPOCH regimen may improve the overall prognosis of patients.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene)
    |
    TP53 mutation • BCL2 expression • MYC expression • CD79B mutation • CD79B mutation • PIM1 mutation
    |
    Rituxan (rituximab)
    2years
    Disparities in Somatic Mutations and Outcomes in Primary Central Nervous System Lymphoma Comparing Patients of Hispanic and Non-Hispanic Ethnicity (ASH 2022)
    90% of patients received systemic chemotherapy for initial treatment, with 41% receiving high dose Methotrexate, Rituximab and Temozolomide... We identified highly recurrent genetic alterations in PCNSL. Our data suggest that some heterogeneity in the most frequent mutations in PCNSL may be related to ethnicity. Hispanic patients in our study have better 2-year OS; however, the data is limited by the retrospective analysis and the small patient number.
    Clinical
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • CD79B (CD79b Molecule) • CARD11 (Caspase Recruitment Domain Family Member 11) • PIM1 (Pim-1 Proto-Oncogene)
    |
    TP53 mutation • MYD88 mutation • CDKN2A mutation • MYD88 L265P • CD79B mutation • PIM1 mutation
    |
    Rituxan (rituximab) • temozolomide • methotrexate IV
    2years
    Towards a Unified Genetic Classification System for Diffuse Large B-Cell Lymphoma (DLBCL) (ASH 2022)
    We present here a refined classification of DLBCL genetic subgroups that combines previously described classification algorithms and extends it to allow classification of more tumors into additional subgroups that preserve the major divisions of existing systems. This represents an important advancement that will facilitate further understanding of genomic complexity in this disease.
    IO biomarker
    |
    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • PAX5 (Paired Box 5) • PIM1 (Pim-1 Proto-Oncogene) • TNFRSF14 (TNF Receptor Superfamily Member 14) • IRF4 (Interferon regulatory factor 4) • STAT6 (Signal transducer and activator of transcription 6) • TNFRSF18 (TNF Receptor Superfamily Member 18)
    |
    TP53 mutation • MYC rearrangement • MYC translocation • NOTCH2 mutation • PIM1 mutation • TNFRSF14 mutation
    2years
    Intravascular Large B-Cell Lymphoma Genomic Profile Is Characterized by Alterations in Genes Regulating NF-κB and Immune Checkpoints. (PubMed, Am J Surg Pathol)
    Our results confirm the relevance of mutations in B-cell receptor/nuclear factor-κB signaling and immune escape pathways in IVLBCL and identify novel driver alterations. The similar mutational profile in tumors with extravascular dissemination suggests that these cases may also be considered in the spectrum of IVLBCL.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • ETV6 (ETS Variant Transcription Factor 6) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • GNA13 (G Protein Subunit Alpha 13) • PIM1 (Pim-1 Proto-Oncogene) • CCND3 (Cyclin D3) • IRF4 (Interferon regulatory factor 4) • BTG2 (BTG Anti-Proliferation Factor 2)
    |
    PD-L1 expression • MYD88 L265P • CD79B mutation • CD79B mutation • NOTCH2 mutation • PIM1 mutation • MYD88 L265P + CD79B mutation
    over2years
    Molecular characterization of primary central nervous system lymphoma vs non-CNS lymphoma and correlation between mutational profile and treatment response (EANO 2022)
    Overall survival (OS) was calculated from the start of temozolomide (TMZ) or tissue collection to last contact using insurance claims data... When compared to non-CNS lymphomas, PCNSL tumors showed significantly higher mutation rates in MYD88 (70% vs. 7%) , PIM-1 (58% vs. 7%) , CD79B (42% vs.
    Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • MGMT (6-O-methylguanine-DNA methyltransferase) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • CREBBP (CREB binding protein) • CARD11 (Caspase Recruitment Domain Family Member 11) • PIM1 (Pim-1 Proto-Oncogene) • TNFRSF14 (TNF Receptor Superfamily Member 14) • IRF4 (Interferon regulatory factor 4) • TNFRSF18 (TNF Receptor Superfamily Member 18)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • KMT2D mutation • EZH2 mutation • CD79B mutation • CD79B mutation • PIM1 mutation
    |
    temozolomide
    over2years
    Clinical Significance of MYD88 non-L265P Mutations in Diffuse Large B-Cell Lymphoma. (PubMed, Hematol Oncol)
    The progression-free survival (PFS) in patients with DLBCL with MYD88 non-L265P mutation was statistically better than in patients with MYD88 L265P mutation. The interpretation of variants of MYD88 mutation offers a precise guide for the management of DLBCL.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PIM1 (Pim-1 Proto-Oncogene)
    |
    MYD88 mutation • MYD88 L265P • PIM1 mutation
    over2years
    Genomic Mutation Landscape of Primary Breast Lymphoma: Next-Generation Sequencing Analysis. (PubMed, Dis Markers)
    These high-mutant genes detected in PBL indicated a tendency to shorten overall survival (OS) and progression-free survival (PFS), which may lead to poor prognosis. Furthermore, the nuclear factor kappa-B (NF-κB) pathway and related regulatory factors are essential for the development of targeted therapy as well.
    Retrospective data • Journal • Next-generation sequencing
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • TNFAIP3 (TNF Alpha Induced Protein 3) • PIM1 (Pim-1 Proto-Oncogene)
    |
    KMT2D mutation • PIM1 mutation
    over2years
    SUBCLONAL ARCHITECTURE OF CHROMOSOMES REVEALED BY SINGLE-CELL ANALYSIS OF GENE EXPRESSION IN A PATIENT WITH CLONAL EVOLUTION OF RELAPSING/REFRACTORY CLL (EHA 2022)
    Such fact can be exploited to reconstruct chromosomal disruptions in individual cells using scRNAseq and to uncover the subclonal architecture of the disease. Grants: MH-CZ_AZV_NU20-08-00314, MH-CZ_AZV_NV19-03-00091, MEYS-CZ_MUNI/A/1330/2021, MH-CZ_RVO_65269705.
    Clinical • IO biomarker
    |
    TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • BIRC3 (Baculoviral IAP repeat containing 3) • XPO1 (Exportin 1) • PIM1 (Pim-1 Proto-Oncogene) • ZMYM3 (Zinc Finger MYM-Type Containing 3)
    |
    TP53 mutation • ATM mutation • NOTCH1 mutation • Chr del(11q) • PIM1 mutation • TP53 mutation + ATM mutation
    over2years
    Oncogenic Mutations and Tumor Microenvironment Alterations of Older Patients With Diffuse Large B-Cell Lymphoma. (PubMed, Front Immunol)
    Older DLBCL also manifested reduction in CD4 naïve T and CD8 naïve T cells, and also increased recruitment of exhausted T cells and macrophages, leading to immunosuppressive tumor microenvironment. Our work thus contributes to the understanding of aging-related oncogenic mutations and tumor microenvironment alterations in lymphoma progression, and may provide new insights to mechanism-based targeted therapy in DLBCL.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD79B (CD79b Molecule) • CREBBP (CREB binding protein) • CD4 (CD4 Molecule) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2) • TBL1XR1 (TBL1X Receptor 1)
    |
    TET2 mutation • PIM1 mutation
    almost3years
    The Mutation of BTG2 Gene Predicts a Poor Outcome in Primary Testicular Diffuse Large B-Cell Lymphoma. (PubMed, J Inflamm Res)
    Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy. In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.
    Journal
    |
    NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ETV6 (ETS Variant Transcription Factor 6) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • MSH3 (MutS Homolog 3) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2)
    |
    MSH3 mutation • PIM1 mutation
    almost3years
    PIM1 and CD79B Mutation Status Impacts the Outcome of Primary Diffuse Large B-Cell Lymphoma of the CNS. (PubMed, Front Oncol)
    We developed a new molecular classification to divide CNS DLBCL into CDP and non-CDP groups based on CD79B and PIM1 mutational status. Patients with PIM1 and/or CD79B mutations had favorable long-term survival after high-dose methotrexate-based polychemotherapy.
    Journal • IO biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene)
    |
    BCL2 expression • MYC expression • CD79B mutation • CD79B mutation • PIM1 mutation
    |
    methotrexate • methotrexate IV
    3years
    Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach. (PubMed, PLoS One)
    MD results indicate significant conformational altercations in the structure of PIM1, especially upon F147C mutation. This study provides a significant insight into the PIM1 dysfunction upon single amino acid substitutions, which can be utilized to get insights into the molecular basis of PIM1-associated disease progression.
    Journal
    |
    PIM1 (Pim-1 Proto-Oncogene)
    |
    PIM1 mutation