首页|期刊导航|疑难病杂志|儿童急性淋巴细胞白血病骨髓CASZ1、TAL1表达对维持化疗期间口服6巯基嘌呤耐受性的影响

儿童急性淋巴细胞白血病骨髓CASZ1、TAL1表达对维持化疗期间口服6巯基嘌呤耐受性的影响OA

The effect of CASZ1 and TAL1 expression in bone marrow tissue of children with acute lymphoblastic leukemia on maintaining oral 6-mercaptopurine tolerance during chemotherapy

中文摘要英文摘要

目的 探讨儿童急性淋巴细胞白血病(ALL)骨髓Castor锌指转录因子1(CASZ1)、T细胞急性淋巴细胞白血病蛋白1(TAL1)基因表达对维持化疗期间口服6巯基嘌呤(6-MP)耐受性的影响.方法 选取2022年1月—2024年2月邢台市人民医院小儿血液肿瘤科行6-MP+环磷酰胺+阿糖胞苷(CAT)化疗的ALL患儿94例为ALL组,同期非恶性血液病且骨髓正常的儿童40例为对照组,根据6-MP耐受性将ALL患儿分为不耐受亚组46例和耐受亚组48例.采用实时荧光定量PCR检测ALL患儿骨髓组织CASZ1、TAL1表达;Pearson相关分析ALL骨髓组织CASZ1与TAL1表达的相关性;多因素Logistic回归分析影响ALL患儿6-MP化疗耐受性的因素;受试者工作特征(ROC)曲线分析骨髓CASZ1、TAL1表达对ALL患儿6-MP化疗耐受性的预测价值.结果 ALL组骨髓组织CASZ1、TAL1的相对表达量高于对照组(t/P=26.706/<0.001、29.722/<0.001);ALL患儿骨髓组织CASZ1与TAL1表达呈正相关(r/P=0.667/<0.001);中高危 ALL 患儿骨髓组织 CASZ1、TAL1 表达高于低危 ALL 患儿(t/P=12.055/<0.001、13.497/<0.001),二者表达在性别、年龄、免疫分型、是否感染、是否输红细胞、PLT及人粒细胞刺激因子中比较,差异均无统计学意义(P>0.05);临床危险度中高危、CASZ1高、TAL1高是影响ALL患儿6-MP化疗不耐受的独立危险因素[OR(95%CI)=1.508(1.188~1.916),1.377(1.123~1.688),1.359(1.085~1.703)];骨髓组织 CASZ1、TAL1 表达单独及二者联合预测ALL患儿6-MP化疗耐受性的AUC分别为0.878、0.811、0.934,二者联合优于各自单独预测价值(Z/P=4.611/<0.001、5.222/<0.001);骨髓 CASZ1、TAL1 高表达组 ALL 患儿 WBC<1 × 109/L、Neu<0.5× 109/L、PLT<25× 109/L持续时间均长于 CASZ1、TAL1 低表达组(CASZ1:t/P=12.682/<0.001、7.483/<0.001、14.645/<0.001;TAL1:t/P=12.426/<0.001、7.562/<0.001、16.606/<0.001).结论 ALL 患儿骨髓组织 CASZ1、TAL1 mRNA 表达上调,两者与6-MP的耐受性密切相关,是新的评估骨髓抑制的指标.

Objective To investigate the effects of Castor zinc finger 1(CASZ1)and basic helix-loop-helix tran-scription factor TAL1 expression in bone marrow tissue of children with acute lymphoblastic leukemia(ALL)on maintaining oral 6-mercaptopurine(6-MP)tolerance during chemotherapy.Methods Clinical data of 94 children with ALL who under-went 6-MP+cyclophosphamide+cytarabine(CAT)chemotherapy in the Department of Pediatric Hematology and Oncology of Xingtai People's Hospital from January 2022 to February 2024 were selected,and 40 children with non-malignant hemato-logical diseases and normal bone marrow were selected as the control group.Quantitative real-time PCR was used to detect the expression of CASZ1 and TAL1 in bone marrow tissue of children with ALL.Factors influencing 6-MP tolerance during ma-intenance chemotherapy and the value of CASZ1 and TAL1 expression in evaluating 6-MP chemotherapy tolerance were sta-tistically analyzed.Results The relative expression levels of CASZ1 and TAL1 in bone marrow tissue of the ALL group were(3.24±0.54)and(2.98±0.42),respectively,which were significantly higher than those in the control group(0.89±0.20)and(0.91±0.18)(t=26.706,29.722,both P<0.001).The expression of CASZ1 and TAL1 in ALL bone marrow tissue was pos-itively correlated(r=0.667,P<0.001).The expression levels of CASZ1 and TAL1 in bone marrow tissue of children with ALL were significantly higher in the high-risk group than in the low-risk group(t=12.055,13.497,both P<0.001).There were no statistically significant differences in the expression of these two markers with respect to gender,age,treatment regimen,im-munophenotype,infection status,red blood cell transfusion status,platelet count,or human granulocyte colony-stimulating fac-tor(all P>0.05).High levels of CASZ1 and TAL1 were risk factors for 6-MP chemotherapy intolerance in children with mod-erate-to-high clinical risk ALL[OR(95%CI)=1.508(1.188-1.916),1.377(1.123-1.688),1.359(1.085-1.703)].The AUCs for bone marrow CASZ1 expression,TAL1 expression,and their combination in predicting 6-MP chemotherapy tolerance were 0.878,0.811,and 0.934,respectively.The combination of the two was superior to their individual predictive values(Z=4.611,5.222,both P<0.001).The durations of white blood cell count<1×109/L,absolute neutrophil count<0.5× 109/L,and platelet count<25×109/L in ALL children with high expression of bone marrow CASZ1 and TAL1 were all significantly longer than those in the low expression groups(t=12.426,7.562,16.606,all P<0.05).Conclusion Upregulation of CASZ1 and TAL1 expression in bone marrow tissue of children with ALL is associated with 6-MP tolerance and may serve as novel indicators for evaluating bone marrow suppression.

薛红娟;高伟;张衡璐;夏红;陈丹

054000 河北省邢台市人民医院小儿血液肿瘤科054000 河北省邢台市人民医院小儿血液肿瘤科054000 河北省邢台市人民医院小儿血液肿瘤科054000 河北省邢台市人民医院儿一科054000 河北省邢台市人民医院小儿血液肿瘤科

医药卫生

急性淋巴细胞白血病6-巯基嘌呤Castor锌指转录因子1T细胞急性淋巴细胞白血病蛋白1耐受性儿童

Acute lymphoblastic leukemia6-MercaptopurineCastor zinc finger 1T-cell acute lymphocytic leuke-mia protein 1ToleranceChildren

《疑难病杂志》 2026 (4)

406-411,417,7

河北省医学科学研究课题计划(20220696) Hebei Medical Science Research Project Plan(20220696)

10.3969/j.issn.1671-6450.2026.04.005

评论