&lt;p&gt;Characteristics and Management of &lt;em&gt;TP53&lt;/em&gt;-Mutated Diffuse Large B-Cell Lymphoma Patients&lt;/p&gt;

Qin, Yan; Jiang, Shiyu; Liu, Peng; Yang, Jianliang; Yang, Sheng; He, Xiaohong; Zhou, Shengyu; Gui, Lin; Lin, Jing; Du, Xinhua; Yi, Yuting; Sun, Yan

doi:10.2147/cmar.s269624

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…In humans, mutations in the p53 gene occur in DLBCL patients (about 20%) and are identified in both GCB and ABC subtypes. 48 Whether LMP1 or LMP2A affects p53 mutations in DLBCL remains to be elucidated. Finally, frequent mutations in cellular genes such as ID3 and TCF3 are found in BL and associated with the induction of cell survival mediated by the BCR and the promotion of tumor proliferation through cell cycle transition activated by CDK4/6−cyclin D. 2,8 - 10,27,43 - 46 Mutations in these genes were not changed by LMP1 in our sequence analysis.…”

Section: Discussionmentioning

confidence: 99%

Latent membrane proteins from EBV differentially target cellular pathways to accelerate MYC-induced lymphomagenesis

et al. 2022

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MYC translocations in association with Epstein-Barr virus (EBV) infection are often observed in B-cell lymphomas. A subset of Burkitt lymphoma (BL) express EBV latent membrane protein 1 and 2A (LMP1 and LMP2A) in addition to the typical restricted EBV latent gene expression. EBV-associated DLBCL typically exhibit latency type II or III and express LMP1. Here, we investigate the role of LMP1 in MYC-driven lymphomagenesis in our murine model. λ-MYC mice develop tumors having a "starry-sky" appearance and have abnormal p53 expression that is also observed in human BL. LMP2A/λ-MYC double-transgenic mice develop tumors significantly faster than mice only expressing MYC. Similar to LMP2A/λ-MYC mice, LMP1/λ-MYC mice also have accelerated MYC-driven lymphomagenesis. As observed in LMP2A/λ-MYC mice, p27kip1 was degraded in LMP1/λ-MYC pretumor and tumor B cells. Coexpression of LMP1 and LMP2A resulted in enhancement of B cell proliferation. In contrast to LMP2A, the inhibition of Syk or CDK4/6 activity did not effectively inhibit LMP1-mediated MYC lymphomagenesis. Also in contrast to LMP2A, LMP1 did not lessen abnormal p53 expression in λ-MYC tumors. To investigate the significance of LMP1 expression in human BL development, we reanalyzed RNA-Seq data of primary human BL from previous studies. Interestingly, p53 mutations were less observed in LMP1-expressing BL although they were not significantly changed by EBV infection, indicating LMP1 may lessen p53 mutations in human primary BL. This suggests LMP1 effects in EBV-associated human BL varies from what we observe in our murine model. Finally our studies suggest a novel pathogenic role of LMP1 in lymphomagenesis.

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Section: Discussionmentioning

confidence: 99%

Latent membrane proteins from EBV differentially target cellular pathways to accelerate MYC-induced lymphomagenesis

et al. 2022

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“…TP53 mutations have been shown to be significantly associated with poor overall survival in DLBCL [ 38 , 39 ]. Clipson A et al [ 40 ] also found the significant association of TP53 mutation with poor overall survival in DLBCL with MYC translocation.…”

Section: Discussionmentioning

confidence: 99%

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

Zhang

Fei

et al. 2021

Cancer Cell Int

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Background Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. Methods We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6–56.8%) and 37.5% (95% CI, 24.0–52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. Conclusions DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

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“…Sample sequencing was performed on a Next Seq500 Sequencer (Illumina, Hayward, CA, USA) with pair-end reads at Burning Rock Biotech (Guangzhou, China) or Geneplus-Beijing (Beijing, China). The detailed sequencing procedure was performed as described previously 14 , 15 , 31 .…”

Section: Methodsmentioning

confidence: 99%

Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

Qin¹,

Chen²,

Liu³

et al. 2021

Cancer Biol Med

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Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2 , TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications ( BCL2 GA/AMP ) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2 GA/AMP , TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2 GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2 GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

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<p>Characteristics and Management of <em>TP53</em>-Mutated Diffuse Large B-Cell Lymphoma Patients</p>

Cited by 11 publications

References 48 publications

Latent membrane proteins from EBV differentially target cellular pathways to accelerate MYC-induced lymphomagenesis

Latent membrane proteins from EBV differentially target cellular pathways to accelerate MYC-induced lymphomagenesis

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

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