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BIOMARKER:

BCL2 expression + MYC expression

i
Other names: MYC, bHLHe39, c-Myc, MYCC, V-myc avian myelocytomatosis viral oncogene homolog, BCL2, Bcl-2, PPP1R50, B-cell CLL/lymphoma 2
Entrez ID:
5ms
Zanubrutinib Combined with R-CHOP in Previously Untreated Non-Germinal Center B-Cell (GCB) Diffuse Large B-Cell Lymphoma (DLBCL) Patients with BCL2 and MYC Protein Co-Expression: A Multicenter, Phase II Study (ASH 2023)
Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy is the standard first-line treatment of DLBCL...Previous study has showed that ibrutinib combined with R-CHOP had improved event free survival (EFS) compared with placebo plus R-CHOP in non-GCB DLBCL patients with BCL2 and MYC co-expression (Johnson et al., Blood 2019)...Conclusions At the time of data cut-off 30 Jun 2023, 6 cycles of zanubrutinib combined with R-CHOP regimen was well tolerated and showed a promising response result in untreated non-GCB double-expression DLBCL patients. The study is ongoing and further results will be continuously released.
Clinical • P2 data • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2)
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BCL2 expression • MYC expression • BCL2 expression + MYC expression • BCL2 positive • MYC positive • MYC expression + BCL2 expression
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Imbruvica (ibrutinib) • Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • Brukinsa (zanubrutinib) • vincristine • prednisone
5ms
A Simplified IPI Including BCL2 Identifies IPI 3 Patients with Poor Prognosis – a GLA/ Dshnhl and Lysa Collaboration (ASH 2023)
Deleting the number of extranodal sites and adding BCL2 expression to the original IPI factors as the only readily available biologic marker allows building an IPI model which effectively separates IPI 3 pts in 2 groups with significantly different prognosis. Restricting eligibility for future clinical trials to DLBCL pts with IPI 3 (and IPI 4) who are BCL2-pos. may help to avoid overtreatment of pts well treated with R-CHOP and at the same time better select pts representing a group with truly unmet medical need who are most likely to benefit from experimental therapies.
Clinical • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2)
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BCL2 expression • MYC expression • BCL2 expression + MYC expression • BCL2 positive • MYC rearrangement • BCL2 rearrangement
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Rituxan (rituximab)
1year
Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL co-expressing BCL2 and MYC in the phase 3 PHOENIX trial. (PubMed, Blood Adv)
We assessed whether high BCL2/MYC co-expression by RNA sequencing could identify a patient subset responsive to ibrutinib using baseline biopsies from the PHOENIX trial (NCT01855750), which evaluated the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-GCB DLBCL. Consequently, high BCL2/MYC co-expression identifies a subset of non-GCB DLBCL that may be preferentially responsive to ibrutinib and warrants further investigation. ClinicalTrials.gov NCT01855750.
P3 data • Journal • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD79B (CD79b Molecule)
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MYC overexpression • MYD88 L265P • BCL2 expression • MYC expression • BCL2 expression + MYC expression • CD79B mutation • MYC overexpression + BCL2 overexpression • CD79B mutation • MYC expression + BCL2 expression
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Imbruvica (ibrutinib) • Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine
over1year
Targeting a Novel G-Quadruplex in the CARD11 Oncogene Promoter with Naptho(2,1-b)furan-1-ethanol,2-nitro- Requires the Nitro Group. (PubMed, Genes (Basel))
Most inhibitors, such as ibrutinib, target downstream BCR kinases with often modest and temporary responses for DLBCL patients...Of note, the expression of BCL2 and MYC, two other key oncogenes in DLBCL pathology with known promoter G4 structures, were often concurrently repressed with NSC373981 and the highly potent R158 analog. Our findings highlight a novel approach to treat aggressive DLBCL by silencing CARD11 gene expression that warrants further investigation.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • CARD11 (Caspase Recruitment Domain Family Member 11)
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BCL2 expression • MYC expression • BCL2 expression + MYC expression
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Imbruvica (ibrutinib)
over1year
Machine learning-based prediction of germinal center, MYC/BCL2 double protein expressor status, and MYC rearrangement from whole slide images in DLBCL patients (ESMO 2022)
Methods 565 whole-slide images (WSI) stained with hematoxylin/eosin from the LYSA trial "GHEDI" (Deciphering the Genetic Heterogeneity of Diffuse large B-cell lymphoma in the rituximab era) dataset were analyzed...Conclusions Our study demonstrates the predictive power of DL applied to WSI to predict DLBCL subtypes. Such predictive models could be used to augment pathologists analysis capacities, especially when IHC staining or FISH are not available.
Clinical • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4) • MME (Membrane Metalloendopeptidase)
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BCL2 expression • MYC expression • BCL2 expression + MYC expression • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement • IRF4 expression
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Rituxan (rituximab)
almost2years
OUTCOMES BY BCL2 AND MYC EXPRESSION AND REARRANGEMENTS IN UNTREATED DIFFUSE LARGE B-CELL LYMPHOMA FROM THE POLARIX TRIAL (EHA 2022)
Conclusion Multivariate analyses support the benefit of Pola-R-CHP in patients with BCL2+ and MYC+ DLBCL. The poor prognostic impact associated with DEL, which was mainly driven by BCL2+, appears reduced in Pola-R-CHP- vs R-CHOP-treated patients.
IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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MYC overexpression • BCL2 overexpression • BCL2 expression • MYC expression • BCL2 expression + MYC expression • MYC overexpression + BCL2 overexpression • MYC rearrangement • BCL2 rearrangement
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Rituxan (rituximab)
2years
Novel BCL2 inhibitors with anti-lymphoma activity (AACR 2022)
Here, we synthesized and tested seven novel BCL2i in DLBCL cells with deregulated BCL2, and splenic marginal zone lymphoma (SMZL) cell lines with acquired resistance to idelalisib, copanlisib or ibrutinib. Using in silico-based drug design complemented by classical and kinetic target-guided synthesis (KTGS) led to the synthesis of seven potential BCL2 inhibitors (BCL2i). We report the in vitro anti-lymphoma activities of novel BCL2i, particularly ST-65, in DLBCL and SMZL cells. Our results suggest that these compounds are structures further exploitable for the design of improved anti-lymphoma drugs.Acknowledgements: The research work was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: 991 to AGT).
IO biomarker
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BCL6 (B-cell CLL/lymphoma 6)
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BCL2 overexpression • BCL2 expression • MYC expression • BCL2 expression + MYC expression • MYC overexpression + BCL2 overexpression • BCL2 translocation
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Imbruvica (ibrutinib) • Aliqopa (copanlisib) • Zydelig (idelalisib)
over2years
Significance of Single-cell Level Dual Expression of BCL2 and MYC Determined With Multiplex Immunohistochemistry in Diffuse Large B-Cell Lymphoma. (PubMed, Am J Surg Pathol)
Moreover, the advantage of determining DUEL status by dual-color immunohistochemistry was shown by more robust classification and more homogeneous high-risk subgroup patient identification in both training (n=271) (OS: P<0.0001; EFS: P<0.0001) and validation sets (n=82) (OS: P=0.0087; EFS: P<0.0001). This concept of DUEL is more consistent with carcinogenesis and has greater practical utility, hence it may provide a better basis for both basic and clinical research for the development of new therapeutics.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1)
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BCL2 expression • MYC expression • BCL2 expression + MYC expression
over2years
First-Line Treatment with R-CHOP Vs Dose-Adjusted R-EPOCH for Double-Expressor Lymphoma: A University of California Hematologic Malignancies Consortium Retrospective Analysis (ASH 2021)
Retrospective studies have reported mixed results with the use of dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) for the treatment of DEL, but the previously largest published retrospective study suggests a clinical benefit in patients <65 years with DEL when compared to R-CHOP. Across multiple subgroups of DEL by age, stage, cell of origin, transformation, triple expression, and MYC-R, BCL2-R and/or BCL6-R, neither regimen demonstrated superior outcomes. Larger randomized, prospective trials are needed to clarify the role of dose-intensified regimens for first-line treatment of DEL.
Retrospective data • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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BCL2 overexpression • BCL2 expression • MYC expression • BCL2 expression + MYC expression • BCL6 rearrangement • BCL2 rearrangement
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Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine
over2years
Impact of Timing and Precision of Histopathological Diagnosis on Outcomes of Patients with Burkitt and High-Grade B-Cell Lymphoma (ASH 2021)
Overall, we identified n=66 patients with suspected diagnosis of BL within the preliminary assessment. Final histopathological results confirmed n=31 patients as BL (Group A), while n=23 patients were described as showing features of both BL and DLBCL (Uncertain & Grey-zone, Group D). Additionally, in n=12 patients the final diagnosis was revised either from DLBCL to BL (n=9, Group B) or B-ALL/BL to DLBCL (n=3, Group C).
Clinical • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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BCL2 overexpression • BCL2 expression • MYC expression • BCL2 expression + MYC expression • MYC rearrangement
over2years
Suppressing Synthesis of the Long Isoform of the Prolactin Receptor Is a Targeted Strategy to Prevent and Treat B Cell Malignancies (ASH 2021)
Of note, no reductions were observed in NK cell viability or MYC levels within NK cells upon LF PRLR knockdown, suggesting that LF PRLR selectively kills B-lymphoblasts without negatively impacting NK homeostasis. Conclusion Our studies identify the specific knockdown of LF PRLR as a potentially safe and targeted strategy to prevent the onset of B cell malignancies in SLE patients and to treat flagrant DLBCL and B-ALL.
IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • IGH (Immunoglobulin Heavy Locus) • PRLR (Prolactin Receptor 2) • RAG1 (Recombination Activating 1)
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MYC overexpression • BCL2 overexpression • BCL2 expression • MYC expression • BCL2 expression + MYC expression • MYC overexpression + BCL2 overexpression