Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53
Abstract Background TP53 mutations have a prognostic significance in relapsed and refractory diffuse large B‐cell lymphoma (rrDLBCL) patients, and their treatment still faces a great challenge. This study aimed to evaluate the prognosis of patients with TP53 mutations (TP53mut) in the context of CAR...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5756 |
| _version_ | 1827259915634212864 |
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| author | Fan Gao Kai Hu Peihao Zheng Hui Shi Xiaoyan Ke |
| author_facet | Fan Gao Kai Hu Peihao Zheng Hui Shi Xiaoyan Ke |
| author_sort | Fan Gao |
| collection | DOAJ |
| description | Abstract Background TP53 mutations have a prognostic significance in relapsed and refractory diffuse large B‐cell lymphoma (rrDLBCL) patients, and their treatment still faces a great challenge. This study aimed to evaluate the prognosis of patients with TP53 mutations (TP53mut) in the context of CAR‐T therapy (Chimeric antigen receptor T‐cell therapy) as well as explore the heterogeneity in their cohort and identify the possible risk factors. Methods A retrospective study was conducted to investigate the clinical characteristics of rrDLBCL patients with TP53 mutations and their prognostic factors, receiving CAR‐T therapy. And the expression level of TP53 and DDX3X, which was an important co‐mutation of TP53 revealed in the cohort, were explored in public databases and cell lines. Results The median overall survival time of 40 patients with TP53 mutations was 24.5 months, while their median progression‐free survival time after CAR‐T was 6.8 months. There were no significant differences in the ORR (objective remission rate, X2 = 3.0498, p > 0.05) and PFS (after CAR‐T therapy) between the patients with wild‐type and mutated TP53 genes after CAR‐T therapy, while the OS of patients with TP53 mutations was significantly worse (p < 0.01). In patients with TP53 mutations, the performance status (ECOG score) was identified as the most important prognostic factor, while the efficacies of induction and salvage treatments were also correlated with the prognosis. Among molecular indicators, the co‐mutations of Chr‐17 and those located on the exon 5 of the TP53 gene showed a tendency for a worse prognosis. Moreover, the patients with TP53‐DDX3X co‐mutations were identified as a subgroup with an extremely bad prognosis. The expression levels of DDX3X and TP53 were explored in a public database and the cell lines with their co‐mutations, which indicated that inhibiting the DDX3X gene could affect the proliferation of rrDLBCL cells and the expression of TP53. Conclusions This study indicated rrDLBCL patients with TP53 mutations was still the group of poor prognosis in the CAR‐T therapy era. CAR‐T therapy can benefit some TP53mut patients, and the performance status (ECOG) might help predict their prognosis. The study also revealed a subgroup of TP53‐DDX3X co‐mutations in rrDLBCL, which showed a strong clinical significance. |
| first_indexed | 2024-03-13T08:56:40Z |
| format | Article |
| id | doaj.art-a37ef9d39b344ceb8975c4ce4166bbdb |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2025-03-22T02:34:10Z |
| publishDate | 2023-05-01 |
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| series | Cancer Medicine |
| spelling | doaj.art-a37ef9d39b344ceb8975c4ce4166bbdb2024-05-04T06:40:56ZengWileyCancer Medicine2045-76342023-05-01129102671027910.1002/cam4.5756Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53Fan Gao0Kai Hu1Peihao Zheng2Hui Shi3Xiaoyan Ke4Department of Hematology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an ChinaDepartment of Adult Lymphoma Beijing Boren Hospital Beijing ChinaDepartment of Adult Lymphoma Beijing Boren Hospital Beijing ChinaDepartment of Adult Lymphoma Beijing Boren Hospital Beijing ChinaDepartment of Hematology Peking University Third Hospital Beijing ChinaAbstract Background TP53 mutations have a prognostic significance in relapsed and refractory diffuse large B‐cell lymphoma (rrDLBCL) patients, and their treatment still faces a great challenge. This study aimed to evaluate the prognosis of patients with TP53 mutations (TP53mut) in the context of CAR‐T therapy (Chimeric antigen receptor T‐cell therapy) as well as explore the heterogeneity in their cohort and identify the possible risk factors. Methods A retrospective study was conducted to investigate the clinical characteristics of rrDLBCL patients with TP53 mutations and their prognostic factors, receiving CAR‐T therapy. And the expression level of TP53 and DDX3X, which was an important co‐mutation of TP53 revealed in the cohort, were explored in public databases and cell lines. Results The median overall survival time of 40 patients with TP53 mutations was 24.5 months, while their median progression‐free survival time after CAR‐T was 6.8 months. There were no significant differences in the ORR (objective remission rate, X2 = 3.0498, p > 0.05) and PFS (after CAR‐T therapy) between the patients with wild‐type and mutated TP53 genes after CAR‐T therapy, while the OS of patients with TP53 mutations was significantly worse (p < 0.01). In patients with TP53 mutations, the performance status (ECOG score) was identified as the most important prognostic factor, while the efficacies of induction and salvage treatments were also correlated with the prognosis. Among molecular indicators, the co‐mutations of Chr‐17 and those located on the exon 5 of the TP53 gene showed a tendency for a worse prognosis. Moreover, the patients with TP53‐DDX3X co‐mutations were identified as a subgroup with an extremely bad prognosis. The expression levels of DDX3X and TP53 were explored in a public database and the cell lines with their co‐mutations, which indicated that inhibiting the DDX3X gene could affect the proliferation of rrDLBCL cells and the expression of TP53. Conclusions This study indicated rrDLBCL patients with TP53 mutations was still the group of poor prognosis in the CAR‐T therapy era. CAR‐T therapy can benefit some TP53mut patients, and the performance status (ECOG) might help predict their prognosis. The study also revealed a subgroup of TP53‐DDX3X co‐mutations in rrDLBCL, which showed a strong clinical significance.https://doi.org/10.1002/cam4.5756chimeric antigen receptor T‐cell therapyDDX3X mutationdiffuse large B‐cell lymphomasequencingTP53 gene |
| spellingShingle | Fan Gao Kai Hu Peihao Zheng Hui Shi Xiaoyan Ke Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53 Cancer Medicine chimeric antigen receptor T‐cell therapy DDX3X mutation diffuse large B‐cell lymphoma sequencing TP53 gene |
| title | Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53 |
| title_full | Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53 |
| title_fullStr | Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53 |
| title_full_unstemmed | Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53 |
| title_short | Characteristics and prognosis of rrDLBCL with TP53 mutations and a high‐risk subgroup represented by the co‐mutations of DDX3X‐TP53 |
| title_sort | characteristics and prognosis of rrdlbcl with tp53 mutations and a high risk subgroup represented by the co mutations of ddx3x tp53 |
| topic | chimeric antigen receptor T‐cell therapy DDX3X mutation diffuse large B‐cell lymphoma sequencing TP53 gene |
| url | https://doi.org/10.1002/cam4.5756 |
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