TP53 deletion

P1/2, N=73, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

Future studies should explore long-term durability beyond 5 years and validate MRD thresholds for treatment cessation. National Nature Science Foundation of China, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Xisike Clinical Oncology Research Foundation.

P2, N=235, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.

In conclusion, CAR-T cell therapy targeting GPRC5D is highly effective and well-tolerated in patients with RRMM, especially those with high-risk factors. Further studies with larger cohorts and longer follow-up periods are needed to validate the clinical application of GPRC5D-targeted CAR-T cell therapy in RRMM, particularly for patients who have failed BCMA-targeted therapies.

Post-hoc analysis of the OCEAN trial melflufen-treated del(17p) patient population also demonstrated favorable progression free survival compared to pomalidomide-treated cohort. Our insights into the molecular mechanisms of melflufen activity in TP53-/- myeloma support its clinical efficacy and application in the del(17p) and TP53-/- patient population.Trial registration NCT03151811, registration 2017-05-09.

Autologous CD19 CAR T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. Sequential administration of CAR20/22/19 T cells may have reduced the antigen escape relapse in DLBCL. For patients with DLBCL relapse after allo-HSCT, larger trials are required to validate the safety and effectiveness of pseudoallogeneic CAR-T therapy as well as its ability to lower the rate of antigen escape relapse.

A notable feature of the HRS-like cells in this case is the gain of markers associated with CHL, such as CD30 and CD15. This immunophenotypic shift highlights the concept of lymphoma plasticity, where the tumor cells evolve in response to selective pressures, such as CAR T cell therapy.

Integrating methylation markers SHOX2, HOXA9, Septin9, and RASSF1A exhibits significant diagnostic potential in pleural effusion lymphoma, especially within DLBCL subgroups. These markers could prove valuable in identifying high-risk subgroups and guiding clinical decision-making.

BAP1, MTAP, and NF2/merlin were retained by immunohistochemistry, but p53 was overexpressed by immunohistochemistry in the flat mesothelioma in situ, papillary mesothelioma in situ, and invasive mesothelioma. Almost all cases of mesothelioma in situ that have been previously described have a BAP1 mutation/deletion; this is the first example of mesothelioma in situ associated with a TP53 mutation, and suggests that staining for p53 may be useful in evaluating potential mesothelioma in situ cases.

Germline genetic testing based solely on MPC had a diagnostic yield comparable to guideline-based testing. MPC could be considered as an independent criterion for genetic testing to improve the identification of a hereditary cancer predisposition.

We herein report a case of the leukemic phase of chronic lymphocytic leukemia (CLL)-type lymphoma that abruptly developed 12 months after the initial diagnosis of autoimmune hemolytic anemia (AIHA), in which retrospective immunohistochemistry and next-generation sequencing (NGS) revealed that (1) lymphoma with a CLL-type immunophenotype underlay the development of secondary AIHA, (2) complete loss of TP53 function by double-hit TP53 abnormalities (TP53 deletion and mutation) was secondarily acquired, and (3) complete loss of TP53 function could have contributed to clinical manifestation of transformed lymphoma. Immunohistochemistry for LEF1 and an NGS analysis may help physicians precisely diagnose CLL-type lymphoproliferation-associated AIHA.