伴PAX5P80R突变的急性B淋巴细胞白血病的临床和分子遗传学特征  

Clinical and molecular genetic characteristics of B-cell acute lymphoblastic leukemia with PAX5P80R

作　　者：吴倩[1] 解珺丹[1] 申真 杨小飞[1] 薛梦星[1] 邓爱玲 窦雪晴 秦天 陈苏宁[1] WU Qian;XIE Jundan;SHEN Zhen;YANG Xiaofei;XUE Mengxing;DENG Ailing;DOU Xueqing;QIN Tian;CHEN Suning(Department of Hematology,The First Affiliated Hospital of Soochow University,Jiangsu Instituteof Hematology,National Clinical Research Center for Hematologic Diseases,Suzhou,Jiangsu,215006,China;Soochow Hopes Hematology Hospital)

机构地区：[1]苏州大学附属第一医院血液内科江苏省血液研究所国家血液系统疾病临床医学研究中心,江苏苏州215006 [2]苏州弘慈血液病医院

出　　处：《临床血液学杂志》2025年第3期178-183,190,共7页Journal of Clinical Hematology

基　　金：国家自然科学基金(No:82400188、82170158)。

摘　　要：目的:分析伴PAX5P80R突变的急性B淋巴细胞白血病(B-ALL)的临床和分子遗传学特征,探索该亚型患者治疗方案与预后的关系。方法:回顾性研究2019年9月—2024年11月苏州大学附属第一医院和苏州弘慈血液病医院收治的B-ALL患者中,伴PAX5P80R突变患者的临床资料。结果:936例B-ALL患者中,10例(1.1%)伴PAX5P80R。其中,男性占80%,初诊中位年龄为35.5(14.0~59.0)岁。10例患者均表达CD10、CD19,其中7例患者还表达CD34和CD38。4例患者合并染色体异常,所有患者融合基因均阴性。7例患者合并22个共突变,其中NRAS最为常见(5/7)。异常核型患者伴有2个以上共突变比例明显高于正常核型患者(100.0%vs 16.6%,P=0.02)。经过基于VP(长春地辛+地塞米松)方案的多药联合诱导化疗后,10例患者均达到形态学完全缓解(CR),其中5例(50%)流式微小残留病(MFC-MRD)阴性(<0.01%);巩固治疗期间,4例在CR1期间行异基因造血干细胞移植(allo-HSCT)的患者存活,3例患者化疗期间出现复发(2例死亡,1例经移植、嵌合抗原受体T细胞治疗后存活),2例化疗患者无复发生存[1例儿童患者已完成中国儿童白血病协作组-2015化疗方案(CCCG-ALL-2015),1例拟行allo-HSCT],其余1例患者失访。中位随访时间42(2~63)个月,5年总生存率(OS)及无复发生存率(PFS)分别为75%(95%CI 0.153~0.503)和62.5%(95%CI 0.171~0.365),中位OS和PFS均未达到。结论:PAX5P80R突变的B-ALL对诱导化疗敏感,总体预后良好,但合并其他高危遗传学异常对预后的影响有待进一步探索。Objective:To analyze the clinical and molecular genetic features of B-cell acute lymphoblastic leukemia(B-ALL)with PAX5P80Rand explore the correlation between treatment approaches and clinical outcomes.Methods:A retrospective study was conducted on clinical data of B-ALL patients with PAX5P80Rmutation admitted to the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital from September 2019to November 2024.Results:In a cohort of 936patients diagnosed with B-ALL,10cases(1.1%)were identified PAX5P80Rmutation.Among these cases,80%were male,with a median age of 35.5years at diagnosis(range 14-59years).All 10patients expressed CD10and CD19,with 7of them also expressing CD34and CD38.Four patients had chromosomal abnormalities,while all patients tested negative for fusion genes.Seven patients had 22co-mutations,with NRAS being the most common(5/7).The proportion of patients with more than two co-mutations was significantly higher in those with abnormal karyotypes compared to those with normal karyotypes(100.0%vs 16.6%,P=0.02).Following induction chemotherapy based with VP regimen,all patients achieved complete remission(CR),with a 50%rate of minimal residual disease(MRD)negativity by flow cytometry.During consolidation therapy,4patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)in CR1.Of the remaining patients,3experienced relapse(2deaths,1survived after allo-HSCT and chimeric antigen receptor T cell therapy),while 2were still alive without recurrence(1pediatric patient completed the CCCG-ALL-2015protocol,and 1was planning for allo-HSCT).One patient was lost to follow-up.The median follow-up was 42months(range 2-63months),with 5-year overall survival(OS)and progression-free survival(PFS)rates of 75%(95%CI 0.153-0.503)and 62.5%(95%CI 0.171-0.365),respectively.The median OS and PFS were not reached.Conclusion:B-ALL with PAX5P80Rshows positive responses to induction chemotherapy,with an overall good prognosis.However,the impact of concomitant high-risk genetic abn

关 键 词：急性淋巴细胞白血病 PAX5P80R 标危 难治/复发 嵌合抗原受体T细胞 异基因造血干细胞移植 

分 类 号：R733.71[医药卫生—肿瘤]