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BIOMARKER:

MYD88 mutation

i
Other names: MYD88, MYD88 Innate Immune Signal Transduction Adaptor, Myeloid Differentiation Primary Response Protein MyD88, Myeloid Differentiation Primary Response Gene (88), Myeloid Differentiation Primary Response 88, Mutant Myeloid Differentiation Primary Response 88, MYD88D
Entrez ID:
Related biomarkers:
22h
Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia. (PubMed, Curr Hematol Malig Rep)
The findings of the RAINBOW trial (NCT046152), comparing the dexamethasone, rituximab, and cyclophosphamide (DRC) regimen to the first-generation, ibrutinib are awaited, but more studies are needed to draw definitive conclusions on the comparative efficacy of chemoimmunotherapy and BTKi. Complete response is elusive with BTKi, and combination regimens to improve upon the efficacy and limit the treatment duration are also under evaluation in WM.
Review • Journal • IO biomarker
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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MYD88 mutation • MYD88 L265P • BTK C481 • MYD88 wild-type
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Imbruvica (ibrutinib) • Rituxan (rituximab) • cyclophosphamide
7d
Dasatinib In Waldenström Macroglobulinemia (clinicaltrials.gov)
P1, N=3, Terminated, Jorge J. Castillo, MD | Recruiting --> Terminated; Lack of efficacy
Trial termination
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PLCG2 (Phospholipase C Gamma 2)
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MYD88 mutation
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dasatinib • Imbruvica (ibrutinib)
1m
Mutational Landscape and Clinicopathologic Features of Plasmablastic Lymphoma (USCAP 2024)
In conclusion, our findings shed light on the unique molecular complexity of PBL, unveiling its mutational landscape and potential therapeutic targets. Due to the rarity of PBL, further research with a more extensive sample size is essential to completely elucidate the mutational landscape of PBL.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TNFRSF8 (TNF Receptor Superfamily Member 8) • STAT3 (Signal Transducer And Activator Of Transcription 3) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SDC1 (Syndecan 1) • TCF3 (Transcription Factor 3) • CCND3 (Cyclin D3) • CD79A (CD79a Molecule) • TNFRSF13B (TNF Receptor Superfamily Member 13B)
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KRAS mutation • KRAS G12V • MYD88 mutation • KRAS G12 • KRAS G13 • PDGFRA mutation • STAT3 mutation
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Archer® FusionPlex® Lymphoma
2ms
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
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PIM1 (Pim-1 Proto-Oncogene)
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MYD88 mutation • PIM1 mutation
2ms
Biomarker analysis of the ASPEN study comparing zanubrutinib to ibrutinib in patients with Waldenström Macroglobulinemia. (PubMed, Blood Adv)
In TP53MUT, compared to ibrutinib, zanubrutinib-treated patients had higher VGPR+CR (34.6% vs 13.6%, P<0.05), numerically improved MRR (80.8% vs 63.6%, P=0.11), and longer PFS (not reached vs 44.2 months, HR=0.66, P=0.37). Collectively, WM patients with CXCR4MUT or TP53MUT had worse prognosis compared to patients with WT alleles and zanubrutinib led to better clinical outcomes.
Journal
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TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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TP53 mutation • ARID1A mutation • MYD88 mutation • CXCR4 mutation • MYD88 wild-type
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Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
2ms
IκBζ is a dual-use coactivator of NF-κB and POU transcription factors. (PubMed, Mol Cell)
This finding is reinforced by epigenomic analysis of MYD88-mutant lymphoma cells, which revealed colocalization of IκBζ with the POU TF OCT2 and NF-κB:p50 at hundreds of DNA elements harboring octamer and κB motifs. These results suggest that IκBζ is a transcriptional coactivator that can amplify and integrate the output of NF-κB and POU TFs at inducible genes in immune cells.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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MYD88 mutation
2ms
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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MYD88 mutation
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Imbruvica (ibrutinib)
3ms
How we use Genomics and BTK-Inhibitors in the Treatment of Waldenstrom Macroglobulinemia. (PubMed, Blood)
The cBTK-i zanubrutinib shows greater response activity and/or improved PFS in wild-type MYD88, mutated CXCR4, or altered TP53 patients...For patients with acquired resistance to c-BTKi, newer options include the non-covalent BTK-inhibitor pirtobrutinib or the BCL2 antagonist venetoclax. Combinations of BTK-inhibitors with chemoimmunotherapy, CXCR4 and BCL2 antagonists have advanced and are discussed. Algorithms for positioning BTK-inhibitors in treatment-naïve and previously treated WM patients based on genomics, disease characteristics, and co-morbidities are presented.
Journal • IO biomarker
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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TP53 mutation • MYD88 mutation • CXCR4 mutation • MYD88 mutation + CXCR4 mutation • CXCR4 S338X • MYD88 wild-type
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Venclexta (venetoclax) • Brukinsa (zanubrutinib) • Jaypirca (pirtobrutinib)
3ms
Bing-Neel syndrome: a rare neurological complication of Waldenström macroglobulinaemia. (PubMed, BMJ Case Rep)
The patient was initially treated with ibrutinib, before transitioning to zanubrutinib. However, she developed disease progression necessitating radiotherapy with lenalidomide and rituximab maintenance therapy, which achieved remission. This case sheds light on the diagnosis and management of a very rare complication of a rare disease.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
|
MYD88 mutation
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Imbruvica (ibrutinib) • Rituxan (rituximab) • lenalidomide • Brukinsa (zanubrutinib)
3ms
Challenging diagnosis of IgM multiple myeloma. (PubMed, BMJ Case Rep)
IgM monoclonal gammopathies such as IgM myeloma and Waldenström macroglobulinaemia are distinct haematological conditions; however, differentiating between these entities can often present as a challenge.In this review, we explore the challenging diagnosis and treatment of IgM myeloma in a patient presenting with unexplained macrocytic anaemia, elevated serum protein and IgM levels in the absence of t(11;14) and lytic bone lesions that are classically associated with the diagnosis of IgM myeloma. The diagnosis was established based on 40% monoclonal plasma cell population on a bone marrow biopsy, gain of 1q21 on fluorescence in situ hybridisation, cyclin D1 positivity and absence of MYD88 mutation.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CCND1 (Cyclin D1)
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Chr t(11;14) • MYD88 mutation
3ms
"Quadruple-hit" primary testicular diffuse large B-cell lymphoma with MYD88 L265P mutation, IGH::MYC, and IRF4- and BCL6-rearrangements. (PubMed, J Hematop)
Gene expression profiling demonstrated an activated B-cell expression profile. This case highlights the genetic complexity of DLBCL arising in the testis and questions the clinical significance of the identified genetic abnormalities.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
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MYD88 mutation • MYD88 L265P • BCL6 rearrangement
3ms
Molecular Analysis of Liquid Vitreous Biopsy Reveals Occult Lymphoma Following Cytology-Negative Biopsies of the Brain and Vitreous. (PubMed, Ocul Immunol Inflamm)
Only after autopsy of her brain was histopathological and immunohistochemical evidence of PCNSL confirmed. This case illustrates the unique contribution of liquid biopsy neuropathology-oriented molecular testing in a challenging case with high clinical suspicion of PCNSL in which gold-standard diagnostic testing failed to yield a diagnosis.
Journal • Biopsy • Cytology
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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MYD88 mutation
3ms
Utility of reverse transcriptase - Multiplex ligation-dependant probe amplification (RT-MLPA) in the molecular classification of Diffuse Large B cell lymphoma (DLBCL) by cell-of-origin (COO). (PubMed, Indian J Pathol Microbiol)
It was found to be reliable, easy to perform and standardize, requiring only routine instruments available in most molecular laboratories. The RT-MLPA assay therefore provides an alternative for laboratories that would require subtyping of DLBCL, NOS cases in the absence of an access to GEP or other instrument intensive methods.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
|
MYD88 mutation
4ms
Recurrent mutations in Refractory/Relapsed Diffuse Large B cell Lymphoma by targeted gene sequencing. (PubMed, Cytogenet Genome Res)
Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.
Journal
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TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TNFAIP3 (TNF Alpha Induced Protein 3) • CD58 (CD58 Molecule)
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TP53 mutation • NOTCH1 mutation • MYD88 mutation • EZH2 mutation
4ms
An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma. (PubMed, Blood Adv)
The BTK inhibitor-mediated disruption of these signaling complexes translated into a selective ibrutinib sensitivity of lymphomas harboring combined Cd79b and Myd88 mutations. Altogether, this in-depth cross-species comparison provides a framework for the development of molecularly targeted therapeutic intervention strategies in DLBCL.
Preclinical • Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • MALT1 (MALT1 Paracaspase) • PRDM1 (PR/SET Domain 1) • TBL1XR1 (TBL1X Receptor 1)
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MYD88 mutation • CD79B mutation • CD79B mutation
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Imbruvica (ibrutinib)
4ms
Establishment of the Bcwm.2 Cell Line As a BTK-Inhibitor Resistant, BCL2 Inhibitor Sensitive in Vitro and In Vivo Study Model for Waldenström's Macroglobulinemia (ASH 2023)
2 cells did not respond to the BTK-inhibitors ibrutinib, zanubrutinib or pirtobrutinib but were sensitive to the BCL2 inhibitor venetoclax. BCWM. 2 represents a novel, BTK-inhibitor resistant, BCL2 inhibitor sensitive WM cell line that demonstrates MYD88 (S243N) and LYN (I297N) somatic activating mutations, and deletions of 6q. BCWM.
Preclinical • IO biomarker
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CD20 (Membrane Spanning 4-Domains A1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • IRF4 (Interferon regulatory factor 4) • SPI1 (Spi-1 Proto-Oncogene) • HDAC5 (Histone Deacetylase 5) • RUNX3 (RUNX Family Transcription Factor 3)
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MYD88 mutation • LYN mutation • IRF4 expression
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Venclexta (venetoclax) • Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • Jaypirca (pirtobrutinib)
4ms
The Incidence, Clinical Application and Prognostic Significance of MYD88 and CXCR4 Mutation in Chinese Patients with Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia (ASH 2023)
NGS was the most sensitive method for detecting CXCR4 mutation. MYD88 mutation had prognostic significance in BTKi-based therapy, while CXCR4 mutation indicated higher tumor burden and inferior survival in BTKi-based therapy.
Clinical
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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MYD88 mutation • MYD88 L265P • CXCR4 mutation • MYD88 mutation + CXCR4 mutation • MYD88 L265P + CXCR4 mutation • MYD88 wild-type
4ms
A Phase 4, Observational Study Evaluating the Efficacy and Safety of the Bruton Tyrosine Kinase Inhibitor (BTKi) Zanubrutinib in Patients with Waldenström Macroglobulinemia (WM) (ASH 2023)
Background and Significance: Zanubrutinib, a next-generation, selective BTKi, is approved for treatment of WM based on data from the phase 3 ASPEN study (NCT03053440), in which zanubrutinib showed a favorable benefit-risk profile vs ibrutinib, a first-generation BTKi, in patients with symptomatic WM (Tam CS, et al. MRR, VGPR+ rate, and ORR will be presented with 95% CIs, and median DOR will be estimated with the Kaplan-Meier method. The study is currently open for enrollment.
Clinical • Observational data • P4 data
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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MYD88 mutation • MYD88 L265P • MYD88 wild-type
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Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
4ms
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
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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)
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PD-L1 expression • MYD88 mutation • MYD88 L265P • PD-1 expression • BCL2 expression • MYC expression • CD79B mutation • PIM1 mutation
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Rituxan (rituximab) • methotrexate IV
4ms
Mutational Landscape of Diffuse Large B-Cell Lymphoma (DLBCL) in Mexican Patients (ASH 2023)
Inclusion criteria: patients > 18 years, diagnosis of DLBCL, without previous treatment and candidate to be treated with RCHOP... This is the first approach to describe the genomic landscape in Latino-american population. The presence of EZH2 and KMT2 mutations were more frequent in female patients with mediastinal and bulky disease. After multivariate analysis, only the presence of EZH2 mutations was the only genomic factor influencing on OS.
Clinical
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TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein)
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TP53 mutation • MYD88 mutation • KMT2D mutation • EZH2 mutation
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Rituxan (rituximab)
4ms
Preliminary Results from a Phase I/II Study of Pomalidomide Plus Rituximab, Ifosfamide, Carboplatin, and Etoposide for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (PRIDE) (ASH 2023)
The addition of the immunomodulatory agent lenalidomide (Len) to rituximab plus ifosfamide-carboplatin-etoposide (RICE) was shown to be feasible with promising efficacy in some studies. The addition of pomalidomide to the widely used RICE salvage regimen is feasible, and results in promising response rates in this DLBCL population that mostly with non-GCB subtype and double expression. MTD was reached and RP2D was determined to be 2 mg. Further studies are needed to evaluate the efficacy of this regimen, particularly in patients with MYD88 mutations.
P1/2 data
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1)
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MYD88 mutation
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carboplatin • Rituxan (rituximab) • lenalidomide • ifosfamide • etoposide IV • pomalidomide
4ms
Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation. (PubMed, Invest Ophthalmol Vis Sci)
Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.
Journal • Liquid biopsy • Next-generation sequencing • Biopsy
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IGH (Immunoglobulin Heavy Locus) • ETV6 (ETS Variant Transcription Factor 6) • IL6 (Interleukin 6) • IL10 (Interleukin 10) • PIM1 (Pim-1 Proto-Oncogene) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
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MYD88 mutation • MYD88 L265P
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LymphoTrack® Dx IGH Assay • LymphoTrack® Dx IGK Assay
4ms
Clinical, biological, electrophysiological and therapeutic profile of patients with anti-MAG neuropathy according to MYD88 and CXCR4 mutations and underlying haemopathy. (PubMed, J Neurol)
MYD88 mutation and underlying haemopathies are not predictive of a more severe disease. However, in cases of resistant and progressive neuropathy, they provide an opportunity to prescribe newly available drugs such as Bruton tyrosine kinase inhibitors.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • NEFL (Neurofilament Light Chain)
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MYD88 mutation • CXCR4 mutation • MYD88 mutation + CXCR4 mutation
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Rituxan (rituximab)
4ms
Ibrutinib and venetoclax as primary therapy in symptomatic treatment naïve Waldenström macroglobulinemia. (PubMed, Blood)
Ibrutinib and venetoclax induced high VGPR rate and durable responses after EOT, though associated with a higher-than-expected rate of ventricular arrhythmia in WM patients leading to early study treatment termination. The trial was funded by Abbvie and Pharmacyclics (NCT04273139).
Journal • IO biomarker
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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MYD88 mutation • CXCR4 mutation
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Venclexta (venetoclax) • Imbruvica (ibrutinib)
5ms
Prognostic impact of MYD88 and TP53 mutations in diffuse large B Cell lymphoma. (PubMed, Ann Hematol)
There was a significant statistical difference for both MYD88 and TP53 with regard to 2-year PFS and 2-year OS rate. Hence, both mutant MYD88 and TP53 can be used in predicting disease progression and overall mortality.
Journal
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TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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TP53 mutation • MYD88 mutation
5ms
In-depth molecular analysis of lymphomas with lymphoplasmacytic differentiation may provide more precise diagnosis and rational treatment allocation. (PubMed, Ann Hematol)
In addition, we report on a novel BIRC3 frameshift mutation in one case of a progressive WM. Our data indicate that patients with LPL/WM might benefit from thorough pathological work-up and detailed molecular analysis in terms of precise diagnosis and targeted treatment allocation.
Journal
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TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BIRC3 (Baculoviral IAP repeat containing 3)
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TP53 mutation • MYD88 mutation
5ms
A Phase 1b study of pembrolizumab, ibrutinib and rituximab in recurrent/refractory (RR) primary central nervous system lymphoma (PCNSL) (SNO 2023)
The combination of pembrolizumab, ibrutinib and rituximab is well-tolerated with manageable side effects and encouraging efficacy. The phase 2 portion of the study is open.
P1 data • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PD-1 (Programmed cell death 1) • BTK (Bruton Tyrosine Kinase) • CD79B (CD79b Molecule) • PD-L2 (Programmed Cell Death 1 Ligand 2)
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MYD88 mutation • CD79B mutation
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Keytruda (pembrolizumab) • Imbruvica (ibrutinib) • Rituxan (rituximab)
5ms
Clonal Relationship and Mutation Analysis in Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Associated With Diffuse Large B-cell Lymphoma. (PubMed, Hemasphere)
Together, we demonstrate variable clonal B-cell dynamics in LPL/WM patients developing DLBCL, and the occurrence of clonally unrelated DLBCL in about one-quarter of LPL/WM patients. Moreover, we identified commonly mutated genes upon DLBCL transformation, which together with preserved mutations already present in LPL characterize the mutational landscape of DLBCL occurrences in LPL/WM patients.
Journal
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TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD79B (CD79b Molecule) • CARD11 (Caspase Recruitment Domain Family Member 11) • TNFAIP3 (TNF Alpha Induced Protein 3) • PIM1 (Pim-1 Proto-Oncogene) • BTG1 (BTG Anti-Proliferation Factor 1) • BTG2 (BTG Anti-Proliferation Factor 2)
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TP53 mutation • MYD88 mutation • CXCR4 mutation • CD79B mutation • TNFAIP3 mutation • BTG1 mutation • CD79B mutation + TNFAIP3 mutation
5ms
Deciphering the Immune Microenvironment in Waldenstrom's Macroglobulinemia (ASH 2023)
CD40/CD40L blockade led to inhibition of WM cell growth. Overall our studies have demonstrated the existence of a Treg-mediated immunosuppressive phenotype in WM, which can be therapeutically reversed by blocking the CD40L/CD40 axis to inhibit WM cell growth.
IO biomarker
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • FOXP3 (Forkhead Box P3) • CD40LG (CD40 ligand) • TNFSF14 (TNF Superfamily Member 14)
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MYD88 mutation • CXCR4 mutation
5ms
Development of Syngeneic Murine Cell Lines of Germinal Center-Derived B-Cell Lymphomas (ASH 2023)
These cell lines serve as a preclinical tool to test novel therapeutic strategies and develop a deeper understanding of the molecular mechanisms driving lymphomagenesis, therapeutic response, and resistance in genetically defined subtypes of GC-derived B-cell lymphomas. Most importantly, this resource meets a critical need in the field for syngeneic models of lymphoma to study disease progression and precision therapy in immunocompetent mice.
Preclinical • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • KMT2D (Lysine Methyltransferase 2D) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • SDC1 (Syndecan 1) • RAG1 (Recombination Activating 1)
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MYD88 mutation • MYC overexpression • BCL2 overexpression • MYC expression • MYC overexpression + BCL2 overexpression • EZH2 Y641
5ms
Validation of Circulating Tumor DNA As an Alternative to Tumor Tissue Biopsy in Genotyping across Multiple Lymphoma Subtypes (ASH 2023)
Conclusion In the present study, recurrent mutations across a variety of lymphoma subtypes were identified by ctDNA based genotyping, which were in high concordance with tDNA based genotyping. These data demonstrated that ctDNA based genotyping is a reliable noninvasive alternative to tumor tissue biopsy for molecular profiling of lymphoma patients, especially for patients whose tissues are not accessible for genotyping.
Circulating tumor DNA • Biopsy
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TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • KMT2C (Lysine Methyltransferase 2C) • CREBBP (CREB binding protein) • CARD11 (Caspase Recruitment Domain Family Member 11) • RHOA (Ras homolog family member A) • PIM1 (Pim-1 Proto-Oncogene) • SOCS1 (Suppressor Of Cytokine Signaling 1) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
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ATM mutation • DNMT3A mutation • MYD88 mutation • TET2 mutation • CD79B mutation
5ms
Lymphoplasmacytic Lymphoma: An Atypical Presentation with IgG Monoclonal Gammopathy (ASH 2023)
He received one cycle of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone), followed by seven cycles of KCD (Carfilzomib, Cyclophosphamide, Dexamethasone) and Rituximab...The patient was treated with Acalabrutinib, and his anemia, epistaxis, and coagulopathy resolved...In contrast to our patient, who has LPL with IgG Monoclonal gammopathy, approximately 95 percent of LPL patients have IgM Monoclonal gammopathy, which corresponds with WM. As a result, clinicians should be on the lookout for LPL that lacks an IgM Monoclonal Paraprotein.
IO biomarker
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CD20 (Membrane Spanning 4-Domains A1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD38 (CD38 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • SDC1 (Syndecan 1) • MME (Membrane Metalloendopeptidase) • ITGAX (Integrin Subunit Alpha X) • FCER2 (Fc Fragment Of IgE Receptor II)
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CD20 positive • MYD88 mutation • MYD88 L265P • CXCR4 mutation • CD38 positive • SDC1 positive
|
Rituxan (rituximab) • bortezomib • cyclophosphamide • Calquence (acalabrutinib) • carfilzomib
5ms
Treatment Selection and Clinical Outcomes in Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia (LPL/WM) - a Single Center Analysis (ASH 2023)
In our single center experience, chemoimmunotherapy combination with Bendamustine-Rituximab is the most used treatment choice in first line settings followed by single agent anti-CD20 therapy and BTKi. Although Multivariate Cox Regression analysis failed to show statistically significant difference in PFS, there is a tendency towards improved OS in the chemoimmunotherapy subgroup (p=0.08). The shorter PFS in BTKi group is likely due to toxicity of targeted therapy leading to treatment interruption and change of therapy.
Clinical • Clinical data • IO biomarker
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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MYD88 mutation • CXCR4 mutation
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Rituxan (rituximab) • bendamustine
5ms
Changes in Methylation and Chromatin Accessibility Underlie Subtype Classification and Disease Evolution in Waldenström's Macroglobulinemia (ASH 2023)
This is the first independent validation of our previously reported multi-omic driven WM subtype classification. The studies underscore that epigenetic differences underlie the biology of WM subclassification and support a strong role for epigenetic changes driving WM evolution.
IO biomarker
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • PAX5 (Paired Box 5) • LY9 (Lymphocyte Antigen 9) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • SDC1 (Syndecan 1) • CD27 (CD27 Molecule) • ATF1 (Activating Transcription Factor 1) • MXI1 (MAX Interactor 1) • E2F2 (E2F Transcription Factor 2) • FUBP1 (Far Upstream Element Binding Protein 1)
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MYD88 mutation • CXCR4 mutation • MYD88 mutation + CXCR4 mutation • MYD88 wild-type
5ms
Atypical Stem Cell, Pre-B-Cell, T-Cell and Myeloid Gene Expression Characterizes Early Waldenstrom's Macroglobulinemia Clones Which Diminishes with Advancing Disease and Has Therapeutic Implications (ASH 2023)
This analysis suggests that stem cell program reactivation and atypical marker expression characterize early WM clones that are ultimately replaced by clones exhibiting more typical B-cell markers with disease progression. The findings may be relevant to treatment selection and provide a framework for investigating subtype and early/late evolutionary staging in the treatment approach to WM.
IO biomarker
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • CD14 (CD14 Molecule) • CD27 (CD27 Molecule) • FCGR3A (Fc Fragment Of IgG Receptor IIIa) • PRDM1 (PR/SET Domain 1) • VPREB1 (V-Set Pre-B Cell Surrogate Light Chain 1) • XBP1 (X-box-binding protein 1) • CEACAM8 (CEA Cell Adhesion Molecule 8) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • RAG1 (Recombination Activating 1) • IGLL1 (Immunoglobulin Lambda Like Polypeptide 1)
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MYD88 mutation • CD19 expression • CD33 expression
5ms
Identification of MYC-Driven High-Grade B-Cell Lymphoma Using Deep Learning-Based Whole Slide Image Analysis (ASH 2023)
Blood 2020, Varano et al. Nature 2017), which converge on a common phenotype and high-grade morphology (Figure 1B).
IO biomarker
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TP53 (Tumor protein P53) • 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) • IGH (Immunoglobulin Heavy Locus) • CD79B (CD79b Molecule)
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TP53 mutation • MYC rearrangement + BCL2 rearrangement • MYD88 mutation • MYC overexpression • MYC expression • CD79B mutation • MYC rearrangement • CD79B mutation • BCL2 rearrangement
5ms
Clinical Outcomes in Patients with Waldenström Macroglobulinemia (WM) Receiving Ibrutinib on the Phase 3 ASPEN Study ≥1 Year After Transitioning to Zanubrutinib (ASH 2023)
With a median treatment duration of 15 months, worsening of ibrutinib TEAEs of interest for BTKi treatment following transition to zanubrutinib was rare, as was the emergence of new events. Response was maintained or improved in 96% (n=44/46) of efficacy-evaluable patients. While limited by sample size and nonrandomized/ad hoc analysis, data suggest that patients may transition from ibrutinib to zanubrutinib without compromising safety or efficacy; long-term follow-up is ongoing.
Clinical • Clinical data • P3 data
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
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MYD88 mutation
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Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)