Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi最新文献

{"title":"[Somatic and immune profiling of chemotherapy-associated aplastic anemia: a comparison with primary aplastic anemia and cancer without aplastic anemia].","authors":"Y M Zhang, Y X Zhou, Q L Zhuang, B Han","doi":"10.3760/cma.j.cn121090-20251119-00539","DOIUrl":"10.3760/cma.j.cn121090-20251119-00539","url":null,"abstract":"<p><p>This study aimed to characterize the somatic variant candidate gene profile of patients with chemotherapy-associated aplastic anemia (CAA) and compare it with that of patients with cancer without aplastic anemia (non-AA) and primary aplastic anemia (PAA). This study included 24 patients with CAA diagnosed at Peking Union Medical College Hospital from September 2019 to May 2023 (male-to-female ratio of 3∶5; median age, 60 years). Peripheral blood samples were collected for whole-exome sequencing, and the results were compared with publicly available data of patients with non-AA and PAA. A total of 37 111 variants across 9 958 genes were detected. KEGG enrichment analysis revealed that these genes were mainly concentrated in the JAK-STAT and calcium signaling pathways (all <i>P</i><0.01). Regarding human leukocyte antigen (HLA) genes, the mutation frequency of HLA-DRB1 was higher in patients with CAA than in those with non-AA cancer [false discovery rate (FDR) =0.029], whereas the mutation frequencies of HLA-A (FDR=0.082) and HLA-C (FDR=0.058) were lower than in those with PAA. For myeloid disease-related genes, compared with patients with non-AA cancer, those with CAA had higher mutation frequencies in 198 genes, including BRCA2 (FDR=0.032) and ASXL1 (FDR=0.047), and lower frequencies in SAA2 (FDR=0.049), TP53 (FDR=0.045), and PIK3CA (FDR=0.049). Compared with patients with PAA, those with CAA had higher mutation frequencies in 213 genes, including BRCA2 (FDR=0.068) and ATRX (FDR=0.072), and lower frequencies in 14 genes, including ASXL1 (FDR=0.045) and DNMT3A (FDR=0.078). In conclusion, the somatic variant profile of CAA significantly differs from that of non AA cancer and PAA: its degree of immune abnormality is higher than that in non-AA cancer but milder than that in PAA; it shows a higher potential for myeloid evolution than non-AA cancer, but its transformation mechanism is more complex than that of PAA, being influenced by multiple factors including primary tumor characteristics and myeloid gene variants.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"485-489"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Chinese expert consensus on the diagnosis and treatment of elderly patients with mantle cell lymphoma (2026)].","authors":"","doi":"10.3760/cma.j.cn121090-20260207-00084","DOIUrl":"10.3760/cma.j.cn121090-20260207-00084","url":null,"abstract":"<p><p>Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma that predominantly occurs in elderly patients. In China, the proportion of elderly patients with MCL is increasing with the aging of the general population. The emergence of new targeted drugs and novel approaches has changed the treatment patterns and prognosis of MCL. Meanwhile, due to poor tolerance, elderly patients require individualized treatment strategies based on a comprehensive geriatric assessment. Therefore, the Lymphoid Disease Group of the Chinese Society of Hematology, Chinese Medical Association, and the Lymphatic Disease Society of the Chinese Medical Education Association convened relevant experts to formulate this consensus, to improve the diagnosis and treatment levels of elderly patients with MCL in China.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"424-432"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148398082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prognostic analysis of NUP98 rearrangement in patients with pediatric acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation].","authors":"H F Wang, G H Hu, L Bai, P Suo, F Zhang, Y X Zuo, K Y Liu, L P Xu, Y Wang, Y Q Sun, X X He, X H Zhang, X J Huang, Y F Cheng","doi":"10.3760/cma.j.cn121090-20251109-00515","DOIUrl":"10.3760/cma.j.cn121090-20251109-00515","url":null,"abstract":"<p><p><b>Objective:</b> To analyze the prognosis and impact of NUP98 rearrangements (NUP98-r) pre- and post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with pediatric acute myeloid leukemia (pAML) with NUP98-r who underwent allo-HSCT. <b>Methods:</b> This was a retrospective, single-arm, observational cohort study. This study enrolled patients with pAML with NUP98-r who underwent allo-HSCT at Peking University People's Hospital from April 2018 to October 2024. The clinical characteristics, NUP98-r status pre- and post-allo-HSCT, relapse, and survival outcomes of the patients were collected. The impact of NUP98-r status pre- and post-allo-HSCT on prognosis was analyzed. <b>Results:</b> Among 31 patients with pAML with NUP98-r who underwent allo-HSCT, 16 (51.6%) were males and 15 (48.4%) were females, with a median age of 8 years (range: 2-18 years). The median follow-up time was 35 months (range: 6-66 months). The most common NUP98-r subtype was NUP98::NSD1 (22 patients, 71.0%), followed by NUP98::HOXA9 (5 patients, 16.1%). Concurrent FLT3-ITD mutation was present in 18 patients (58.1%) and WT1 mutation in 14 patients (45.2%). Seven patients relapsed post-allo-HSCT, with a median time to relapse of 6 months (range: 3-48 months). The 100-day cumulative incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) was (35.4±8.6) %, and the 3-year cumulative incidence of chronic GVHD was (64.8±9.2) %. The 3-year overall survival, event-free survival (EFS), and cumulative incidence of relapse (CIR) rates were (74.0±9.6) %, (63.9±10.1) %, and (21.3±8.7) %, respectively. The 3-year EFS was higher in patients who were negative for NUP98-r pre-allo-HSCT [ (92.3±7.4) %] than in those positive for NUP98-r [ (42.3± 15.3) %] (<i>P</i>=0.044). The 3-year CIR was higher in patients positive for NUP98-r pre-allo-HSCT [ (34.8±14.6) %] than in those negative for NUP98-r (0) (<i>P</i>=0.036). All patients who were positive for NUP98-r within the first 3 months post-allo-HSCT subsequently relapsed. <b>Conclusion:</b> Allo-HSCT is an effective method for treating NUP98-r pAML, and NUP98-r positivity pre-allo-HSCT is associated with higher CIR and lower EFS. Therefore, efforts should be made to achieve a negative NUP98-r status through treatment before undergoing allo-HSCT.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"458-464"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prognostic impact of WT1 mutations in patients with acute myeloid leukemia].","authors":"Y Zeng, Y Hui, L Yan, Q Y Fang, Y Li, Y Wang, B F Gong, Y T Liu, C C Guo, S Y Li, D Lin, K Q Liu, G J Zhang, C L Zhou, X Y Gong, S W Qiu, B C Liu, Y Wang, Y C Mi, J X Wang, H Wei","doi":"10.3760/cma.j.cn121090-20251222-00608","DOIUrl":"10.3760/cma.j.cn121090-20251222-00608","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the prognostic impact of WT1 mutations in patients with acute myeloid leukemia (AML) . <b>Methods:</b> This was a retrospective cohort study. A total of 1 583 patients with AML who were admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2015 to March 2024 were enrolled in the study, including 1 437 WT1 wild-type patients and 146 (9.2%) carrying WT1 mutations. Clinical characteristics and gene mutation profiles were comprehensively compared between WT1-mutated and wild-type cohorts. Survival analyses were performed on WT1-mutant and WT1 wild-type patients in accordance with the 2022 ELN risk classification and major AML mutation subgroups. The primary outcome measures included overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) . <b>Results:</b> No statistically significant difference in clinical characteristics was found between WT1-mutant and WT1 wild-type patients (all <i>P</i>>0.05). In addition, WT1-mutant AML displayed a unique genomic alteration profile, which is characterized by high frequencies of CEBPA(bZIP) (30.1% <i>vs</i> 15.0%, <i>P</i><0.001) and FLT3-ITD (30.1% <i>vs</i> 19.8%, <i>P</i>=0.036), along with a reduced incidence of NPM1 (11.0% <i>vs</i> 20.4%, <i>P</i>=0.068) and RUNX1::RUNX1T1 (4.8% <i>vs</i> 19.2%, <i>P</i><0.001). Survival analysis of the entire cohort and within the 2022 ELN risk classification revealed no significant differences in OS, RFS, or EFS between WT1-mutated and wild-type groups (all <i>P</i>>0.05). Although WT1 mutations had no significant prognostic impact on different AML subgroups, WT1 mutations were associated with inferior RFS (<i>P</i>=0.042) and EFS (<i>P</i>=0.017) in patients co-mutated with CEBPA(bZIP). Clinical factors, including age, sex, and common AML mutation genes, were incorporated into multivariate Cox regression analyses, which consistently showed that WT1 was not an independent prognostic risk factor (OS: <i>P</i>=0.209, <i>HR</i>=0.796, 95%<i>CI</i>: 0.558-1.137; RFS: <i>P</i>=0.390, <i>HR</i>=1.149, 95%<i>CI</i>: 0.837-1.579; EFS: <i>P</i>=0.180, <i>HR</i>=1.192, 95%<i>CI</i>: 0.922-1.542) . <b>Conclusion:</b> Although WT1 is a common mutation gene in AML, it was not associated with poor prognosis and was not an independent prognostic risk factor in our cohort.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"442-449"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prognostic significance of CEBPA gene mutations in acute myeloid leukemia].","authors":"Z Shen, F H Zhang, W Z Cai, M Tang, H J Shen, X F Yang, S N Chen, S L Feng","doi":"10.3760/cma.j.cn121090-20251111-00520","DOIUrl":"10.3760/cma.j.cn121090-20251111-00520","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the prognostic value of CEBPA gene mutations in patients with newly diagnosed acute myeloid leukemia (AML) . <b>Methods:</b> A retrospective cohort analysis was conducted on the clinical data from 237 CEBPA-mutated AML patients who received intensive chemotherapy induction at the First Affiliated Hospital of Soochow University between January 2016 and December 2024. Clinical characteristics, treatment responses, and prognosis were compared among different mutation subgroups. <b>Results:</b> Among 237 patients, 182 (76.8%) harbored bZIP domain in-frame insertion/deletion mutations (bZIP(InDel)), 13 (5.5%) had bZIP domain missense mutations (bZIP(ms)), and 42 (17.7%) carried other mutation types (Other(mut)). Compared with the latter two groups, patients in the bZIP(InDel) group had a younger age at onset (<i>P</i><0.001), a higher GATA2 mutation rate (<i>P</i><0.001), and lower mutation rates of NPM1 and DNMT3A (both <i>P</i><0.05). After two courses of induction therapy, the bZIP(InDel) group achieved significantly higher complete remission (CR) /CR with incomplete hematologic recovery (CRi) rates and measurable residual disease (MRD) -negative rates than the bZIP(ms) and Other(mut) groups (CR/CRi rates: 99.4% <i>vs</i> 75.0% <i>vs</i> 86.8%, <i>P</i><0.001; MRD-negative rates: 88.6% <i>vs</i> 77.8% <i>vs</i> 66.7%, <i>P</i>=0.008). With a median follow-up of 41 months, the 3-year overall survival (OS) and relapse-free survival (RFS) rates in the bZIP(InDel) group were 90.7% and 72.1%, respectively. Multivariate analysis revealed that CEBPA bZIP(InDel) was an independent favorable prognostic factor for both OS (<i>HR</i>=0.16, 95%<i>CI</i>: 0.06-0.40, <i>P</i><0.001) and RFS (<i>HR</i>=0.31, 95%<i>CI</i>: 0.17-0.57, <i>P</i><0.001). Within the bZIP(InDel) group, patients achieving CR/CRi after one course of induction had a superior 3-year OS rate compared with those achieving CR/CRi after two courses (88.3% <i>vs</i> 48.9%, <i>P</i>=0.050). Although allogeneic hematopoietic stem cell transplantation performed during the first CR (CR1) significantly improved the 3-year RFS rate (89.7% <i>vs</i> 57.6%, <i>P</i><0.001), this benefit did not translate into an OS advantage (<i>P</i>=0.376). Additionally, concurrent KIT mutations were associated with a lower 3-year OS rate (65.6% <i>vs</i> 91.7%, <i>P</i>=0.042), and concurrent CSF3R mutations were associated with a lower 3-year RFS rate (42.9% <i>vs</i> 75.1%, <i>P</i><0.001) . <b>Conclusion:</b> CEBPA bZIP(InDel) confer a distinct prognostic value. Patients in this subgroup derive substantial benefit from chemotherapy; however, the presence of concurrent KIT or CSF3R mutations is frequently associated with unfavorable outcomes.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"450-457"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Autologous hematopoietic stem cell transplantation and sequential CD19 CAR-T therapy for B-lymphoblastic lymphoma at complete remission status: two cases report].","authors":"X N Wang, J Ren, D Wu, P C He","doi":"10.3760/cma.j.cn121090-20251202-00565","DOIUrl":"10.3760/cma.j.cn121090-20251202-00565","url":null,"abstract":"","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"491-492"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148398064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Glofitamab for relapsed/refractory B-cell lymphoma: analysis of efficacy and influencing factors].","authors":"J Cong, C J Wang, N Yao, L Yang, X Li, J Ye, J Yang, L Q Wei, L Wang","doi":"10.3760/cma.j.cn121090-20260104-00002","DOIUrl":"10.3760/cma.j.cn121090-20260104-00002","url":null,"abstract":"<p><p>This single-center retrospective analysis enrolled 32 patients with relapsed/refractory (R/R) B-cell lymphoma who received glofitamab-containing regimens at Beijing Tongren Hospital. Study endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors. The median follow-up duration was 414 (95% <i>CI</i>: 175 - not reached) days, with a 180-day PFS rate of 39.1% (95% <i>CI</i>: 24.0%-63.7%) and a 180-day OS rate of 72.2% (95% <i>CI</i>: 57.5%-90.8%). The ORR was 47.6% and the complete response rate (CRR) was 14.3% in 21 evaluable patients among 25 patients who received glofitamab as salvage therapy. All 6 patients who received glofitamab as bridging therapy achieved a partial response. Univariate analysis revealed the number of prior treatment lines (<i>HR</i>=1.55, 95% <i>CI</i>: 1.15-2.07, <i>P</i>=0.004), prior CAR-T cell therapy (<i>HR</i>=3.35, 95% <i>CI</i>: 1.07-10.49, <i>P</i>=0.038), prior treatment with bendamustine (<i>HR</i>=3.45, 95% <i>CI</i>: 1.05-11.41, <i>P</i>=0.042), and glofitamab monotherapy (<i>HR</i>=4.18, 95% <i>CI</i>: 1.42-12.33, <i>P</i>=0.010) as risk factors for PFS. The incidence of cytokine release syndrome (CRS) was 28.1%, with one patient also developing immune effector cell-associated neurotoxicity syndrome (ICANS), and no grade of ≥3 CRS or ICANS was observed. Glofitamab demonstrates considerable potential in R/R B-cell lymphoma; however, its efficacy as monotherapy is limited in heavily pretreated patients. Combination regimens may better address clinical needs; however, enhanced monitoring for adverse events and supportive care are warranted.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"480-484"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prognostic significance of IKZF1 alterations in acute B-lymphoblastic leukemia and the choice of transplantation strategy].","authors":"X X Ma, E L Jiang","doi":"10.3760/cma.j.cn121090-20250826-00400","DOIUrl":"10.3760/cma.j.cn121090-20250826-00400","url":null,"abstract":"<p><p>Gene alterations in Ikaros family zinc finger protein 1 (IKZF1) are common genetic abnormalities in B-cell acute lymphoblastic leukemia (B-ALL) and are closely associated with an increased risk of relapse and poor prognosis. In this study, the biological functions of the IKZF1 gene and the clinical significance of its various mutation types were systematically elaborated. Accordingly, a comprehensive clinical decision-making framework spanning from diagnosis to post-transplantation management was constructed. This framework provides an in-depth analysis of the pivotal role of immunotherapy as a \"bridge\" to transplantation, innovatively proposes an \"MRD clearance kinetics\" -guided model for deciding on transplantation modalities (allogeneic versus autologous), and defines proactive post-transplantation intervention strategies based on MRD monitoring. Furthermore, this review aims to provide a clear and actionable blueprint for individualized therapy for B-ALL patients with IKZF1 alterations.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"494-499"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Current status and progress in the diagnosis and treatment of monomorphic epitheliotropic intestinal T-cell lymphoma].","authors":"S Su, Y Xiao","doi":"10.3760/cma.j.cn121090-20251128-00557","DOIUrl":"10.3760/cma.j.cn121090-20251128-00557","url":null,"abstract":"<p><p>Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive type of intestinal T-cell lymphoma. With the application of high-throughput sequencing technologies in recent years, the understanding of this entity has become increasingly comprehensive. The World Health Organization classification of lymphoma now recognizes MEITL as a distinct disease entity. However, the extreme rarity of MEITL poses substantial challenges for clinical diagnosis and management, and patient outcomes remain poor. Based on a systematic review of recent literature, this article summarizes the diagnostic criteria of MEITL, integrating pathology and molecular biology; outlines current multimodal treatment approaches centered on surgery, chemotherapy, and hematopoietic stem cell transplantation; and reviews available clinical and translational data to explore the potential role of epigenetic agents, JAK/STAT pathway inhibitors, and other emerging therapeutic strategies in MEITL. This article summarizes the current status and recent advances in the diagnostic and therapeutic strategies for MEITL in clinical practice and provides a reference for the design of future prospective, multicenter clinical studies.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"500-506"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Novel CD6-targeted CAR-T cell therapy for T-cell acute lymphoblastic leukemia: a safe and efficient strategy to prevent fratricide through gene editing].","authors":"Y T Shangguan, L L Xie, W B Liu, R X Gu, Y X Xu, M Wang, J X Wang","doi":"10.3760/cma.j.cn121090-20260130-00068","DOIUrl":"10.3760/cma.j.cn121090-20260130-00068","url":null,"abstract":"<p><p><b>Objective:</b> To explore a novel strategy that addresses the dual challenges of fratricide and on-target off-tumor toxicity in current chimeric antigen receptor T-cell (CAR-T) therapy for T-cell acute lymphoblastic leukemia (T-ALL) and to develop a safe and efficacious anti-T-ALL CAR-T product by identifying a new target and compatible gene-editing approach. <b>Methods:</b> Public single-cell RNA sequencing (scRNA-seq) datasets were utilized to analyze bone marrow cells extracted from patients with T-ALL and healthy donors, evaluating the differential expression profiles of CD6 and CD7. In investigating the endogenous role of CD6 in CAR-T cells, the CRISPR/Cas9 RNP system was first employed in a CD19 CAR-T model to evaluate the impact of CD6 knockout on the phenotype and activation status of CAR-T cells. Subsequently, CD6-knockout, CD6-targeted CAR-T cells (6KO-6CAR) were constructed, and their functional activities were evaluated. <b>Results:</b> scRNA-seq analysis revealed that CD6 is broadly expressed in T-ALL. Compared with the traditional target CD7, which is also expressed in a subset of normal hematopoietic stem/progenitor cells and myeloid cells, CD6 exhibits a more restricted expression profile, exhibiting superior safety characteristics. Studies on the CD19 CAR-T model indicated that CD6 knockout enables CAR-T cells to maintain a superior functional state: their baseline activation level (CD25 expression) was reduced (<i>P</i><0.05) while generating a higher proportion of TNF-α(+)IFN-γ(+) cells (<i>P</i><0.05) upon antigen stimulation. The further constructed 6KO-6CAR cells exhibited potent specific activation (significantly upregulated CD107a expression level, all <i>P</i><0.001) and cytotoxicity (all <i>P</i><0.05) against multiple CD6(+) T-ALL cell lines (MOLT-4, CCRF-CEM, and Jurkat) in vitro. <b>Conclusion:</b> CD6 is a novel therapeutic target for T-ALL with high coverage and a favorable safety profile, and knocking out endogenous CD6 globally optimizes the intrinsic functional state of CAR-T cells. Constructing 6KO-6CAR based on the CRISPR/Cas9 technology addresses fratricide in CAR-T cells while enhancing their antitumor functionality, thereby providing a novel immunotherapy regimen with safety and clinical translational potential for relapsed/refractory T-ALL.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"47 5","pages":"433-441"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}