高级搜索

慢性髓性白血病衍生9号染色体ASS基因缺失与非缺失患者的临床特征

高冠论, 周璇, 许娜, 刘晓力, 魏婷, 李庆山

高冠论, 周璇, 许娜, 刘晓力, 魏婷, 李庆山. 慢性髓性白血病衍生9号染色体ASS基因缺失与非缺失患者的临床特征[J]. 肿瘤防治研究, 2023, 50(3): 283-287. DOI: 10.3971/j.issn.1000-8578.2023.22.0701
引用本文: 高冠论, 周璇, 许娜, 刘晓力, 魏婷, 李庆山. 慢性髓性白血病衍生9号染色体ASS基因缺失与非缺失患者的临床特征[J]. 肿瘤防治研究, 2023, 50(3): 283-287. DOI: 10.3971/j.issn.1000-8578.2023.22.0701
GAO Guanlun, ZHOU Xuan, XU Na, LIU Xiaoli, WEI Ting, LI Qingshan. Clinical Characteristics of Chronic Myeloid Leukemia Patients with Deletion and Non-deletion of ASS Gene on Derivative Chromosome 9[J]. Cancer Research on Prevention and Treatment, 2023, 50(3): 283-287. DOI: 10.3971/j.issn.1000-8578.2023.22.0701
Citation: GAO Guanlun, ZHOU Xuan, XU Na, LIU Xiaoli, WEI Ting, LI Qingshan. Clinical Characteristics of Chronic Myeloid Leukemia Patients with Deletion and Non-deletion of ASS Gene on Derivative Chromosome 9[J]. Cancer Research on Prevention and Treatment, 2023, 50(3): 283-287. DOI: 10.3971/j.issn.1000-8578.2023.22.0701

慢性髓性白血病衍生9号染色体ASS基因缺失与非缺失患者的临床特征

基金项目: 

广东省自然科学基金 2214050003863

广州市卫生健康科技项目 20221A010013

广州市红十字会医院院内课题资助项目 2016-43

详细信息
    作者简介:

    高冠论(1987-),男,硕士,主治医师,主要从事慢性髓性白血病基础及临床研究

    通信作者:

    李庆山(1967-),男,博士,主任医师,主要从事血液系统疾病基础及临床研究,E-mail: drliqingshang@126.com

  • 中图分类号: R733.7

Clinical Characteristics of Chronic Myeloid Leukemia Patients with Deletion and Non-deletion of ASS Gene on Derivative Chromosome 9

Funding: 

Guangdong Natural Science Foundation 2214050003863

Guangzhou Health Science and Technology Fund 20221A010013

Guangzhou Red Cross Hospital Project Fund 2016-43

More Information
  • 摘要:
    目的 

    探讨慢性髓性白血病(CML)慢性期衍生9号染色体ASS基因缺失与非缺失患者的临床特征及疗效。

    方法 

    分析初始治疗方案为伊马替尼并采用BCR/ABL1/ASS1 3色融合探针检测ASS基因是否缺失的CML患者的临床资料,分为缺失组(n=27)和非缺失组(n=92),分析其临床特征、治疗效果及预后。

    结果 

    119例患者平均年龄37.22±12.72岁,缺失组和非缺失组患者的sokal评分差异有统计学意义(χ2=4.304, P=0.038),其他一般特征差异无统计学意义(P > 0.05)。缺失组的3个月完全细胞遗传学反应(CCyR)率及6个月CCyR率、BCR-ABLIS≤ 1%率均低于非缺失组(均P < 0.05)。随访中位数为35.0(3.0~60.0)个月,缺失组PFS低于非缺失组(χ2=4.293, P=0.038),两组OS比较差异无统计学意义(χ2=0.008, P=0.931)。

    结论 

    伊马替尼治疗的CML慢性期患者中ASS基因缺失导致治疗疗效不佳及预后不良,且更易出现疾病进展。

     

    Abstract:
    Objective 

    To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9.

    Methods 

    The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed.

    Results 

    The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ2=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P > 0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABLIS≤ 1% rate in the deletion group were lower than those in the non-deletion group (P < 0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ2=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ2=0.008, P=0.931).

    Conclusion 

    The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression.

     

  • Competing interests: The authors declare that they have no competing interests.
    作者贡献:
    高冠论、周璇:课题设计、资料分析、撰写论文
    许娜、魏婷:数据统计分析与修改核对
    刘晓力、李庆山:拟定写作思路、指导论文撰写与修改
  • 图  1   ASS基因缺失组和非缺失组CML患者无疾病进展(A) 和总生存(B)曲线

    Figure  1   Progression-free survival(A) and overall survival (B) curves of patients with CML in ASS gene deletion and non-deletion groups

    表  1   ASS基因缺失组和非缺失组CML患者临床基线资料比较

    Table  1   Comparison of clinical baseline date of patients with CML in ASS gene deletion and non-deletion groups

    下载: 导出CSV

    表  2   ASS基因缺失组和非缺失组CML患者各时点遗传学反应疗效比较

    Table  2   Comparison of therapeutic effects of genetic responses among patients with CML in ASS gene deletion and nondeletion groups at each time point

    下载: 导出CSV
  • [1]

    Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring[J]. Am J Hematol, 2020, 95(6): 691-709. doi: 10.1002/ajh.25792

    [2]

    Chandran RK, Geetha N, Sakthivel KM, et al. Prognostic Implications of Derivative Chromosome 9 Deletions in Patients with Advanced-Stage Chronic Myelogenous Leukemia[J]. J Environ Pathol Toxicol Oncol, 2018, 37(2): 117-126. doi: 10.1615/JEnvironPatholToxicolOncol.2018026023

    [3]

    Asnafi AA, Deris Zayeri Z, Shahrabi S, et al. Chronic myeloid leukemia with complex karyotypes: Prognosis and therapeutic approaches[J]. J Cell Physiol, 2019, 234(5): 5798-5806. doi: 10.1002/jcp.27505

    [4]

    Li JY, Xu W, Wu W, et al. The negative prognostic impact of derivative 9 deletions in patients who received hydroxyurea treatment for chronic myelogenous leukemia in the chronic phase[J]. Onkologie, 2008, 31(11): 585-589.

    [5] 中华医学会血液学分会. 中国慢性髓性白血病诊断与治疗指南(2016年版)[J]. 中华血液学杂志, 2016, 37(8): 633-639. https://xuewen.cnki.net/CCND-YIYA201610190061.html

    Chinese Society of Hematology, Chinese Medical Association. The guidelines for diagnosis and treatment of chronic myelogenous leukemia in China (2016 edition)[J]. Zhonghua Xue Ye Xue Za Zhi, 2016, 37(8): 633-639. https://xuewen.cnki.net/CCND-YIYA201610190061.html

    [6]

    Deininger MW, Shah NP, Altman JK, et al. Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2020, 18(10): 1385-1415. doi: 10.6004/jnccn.2020.0047

    [7]

    Zhou T, Medeiros LJ, Hu S. Chronic Myeloid Leukemia: Beyond BCR-ABL1[J]. Curr Hematol Malig Rep, 2018, 13(6): 435-445. doi: 10.1007/s11899-018-0474-6

    [8]

    Zhang H, Liu M, Wang X, et al. Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): AnUpdate[J]. Front Genet, 2021, 12: 697009. doi: 10.3389/fgene.2021.697009

    [9] 张朕豪, 王艳芳, 王淼, 等. 应用三色双融合探针检测BCR-ABL融合基因及ASS1基因缺失[J]. 中国实验血液学杂志, 2020, 28(4): 1115-1122. doi: 10.19746/j.cnki.issn1009-2137.2020.04.006

    Zhang ZH, Wang YF, Wang M, et al. [Detection of BCR/ABL Fusion Gene and ASS1 Gene Deletion by Using Tricolor Dual-fusion Probe[J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2020, 28(4): 1115-1122. doi: 10.19746/j.cnki.issn1009-2137.2020.04.006

    [10]

    Fourouclas N, Campbell PJ, Bench AJ, et al. Size matters: the prognostic implications of large and small deletions of the derivative 9 chromosome in chronic myeloid leukemia[J]. Haematologica, 2006, 91(7): 952-955

    [11]

    Egan D, Radich J. Making the diagnosis, the tools, and risk stratification: More than just BCR-ABL[J]. Best Pract Res Clin Haematol, 2016, 29(3): 252-263. doi: 10.1016/j.beha.2016.10.015

    [12]

    Fernandes A, Shanmuganathan N, Branford S. Genomic Mechanisms Influencing Outcome in Chronic Myeloid Leukemia[J]. Cancers (Basel), 2022, 14(3): 620. doi: 10.3390/cancers14030620

    [13]

    Hochhaus A, Baccarani M, Silver RT, et al. European leukemianet 2020 recommendations for treating chronic myeloid leukemia[J]. Leukemia, 2020, 34: 966-984. doi: 10.1038/s41375-020-0776-2

    [14]

    Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia[J]. N Engl J Med, 2017, 376(10): 917-927. doi: 10.1056/NEJMoa1609324

    [15]

    Gorusu M, Benn P, Li Z, et al. On the genesis and prognosis of variant translocations in chronic myeloid leukemia[J]. Cancer Genet Cytogenet, 2007, 173(2): 97-106. doi: 10.1016/j.cancergencyto.2006.10.006

    [16] 董洁, 李薇, 白晶, 等. 9号衍生染色体在慢性粒细胞白血病预后评估中的意义[J]. 吉林大学学报(医学版), 2016, 42(2): 301-305. https://www.cnki.com.cn/Article/CJFDTOTAL-BQEB201602021.htm

    Dong J, Li W, Bai J, et al. Significance of derivative chromosome 9 in evaluation on prognosis of chronic myeloid leukemia[J]. Jilin Da Xue Xue Bao(Yi Xue Ban), 2016, 42(2): 301-305. https://www.cnki.com.cn/Article/CJFDTOTAL-BQEB201602021.htm

    [17]

    Kim DH, Popradi G, Sriharsha L, et al. No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia[J]. Cancer, 2008, 113(4): 772-781. doi: 10.1002/cncr.23607

    [18]

    Švabek ŽT, Josipović M, Horvat I, et al. The incidence of atypical patterns of BCR-ABL1 rearrangement and molecular-cytogenetic response to tyrosine kinase inhibitor therapy in newly diagnosed cases with chronic myeloid leukemia (CML)[J]. Blood Res, 2018, 53(2): 152-159. doi: 10.5045/br.2018.53.2.152

    [19]

    Quintás-Cardama A, Kantarjian H, Shan J, et al. Prognostic impact of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia treated with nilotinib or dasatinib[J]. Cancer, 2011, 117(22): 5085-5093. doi: 10.1002/cncr.26147

    [20]

    Bennour A, Ouahchi I, Ben Youssef Y, et al. Molecular cytogenetic study of derivative chromosome 9 deletion in chronic myeloid leukemia patients[J]. Med Oncol, 2012, 29(2): 1151-1160. doi: 10.1007/s12032-011-9918-8

    [21]

    Jiang Y, Zhang J, Guo D, et al. Entire ABL1 Gene Deletion Without BCR/ABL1 Rearrangement in a Female Patient with B-Cell Precursor Acute Lymphoblastic Leukemia[J]. Onco Targets Ther, 2020, 13: 783-790. doi: 10.2147/OTT.S238336

    [22]

    Bennour A, Sennana H, Laatiri MA, et al. Molecular cytogenetic characterization of variant Philadelphia translocations in chronic myeloid leukemia: genesis and deletion of derivative chromosome 9[J]. Cancer Genet Cytogenet, 2009, 194(1): 30-37. doi: 10.1016/j.cancergencyto.2009.05.010

    [23]

    Kreil S, Pfirrmann M, Haferlach C, et al. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia[J]. Blood, 2007, 110(4): 283-1290.

    [24] 李珍, 张龑莉, 赵慧芳, 等. 伊马替尼联合三氧化二砷治疗伴有ASS基因缺失的Ph+慢性粒细胞白血病的临床研究[J]. 中国实用医刊, 2019, 46(11): 97-99. https://www.cnki.com.cn/Article/CJFDTOTAL-HBZY201812008.htm

    Li Z, Zhang YL, Zhao HF, et al. Effects of imatinib combined arsenic trioxide on Ph+chronic myeloid leukemia patients lacking of ASS genes[J]. Zhongguo Shi Yong Yi Kan, 2019, 46(11): 97-99. https://www.cnki.com.cn/Article/CJFDTOTAL-HBZY201812008.htm

图(1)  /  表(2)
计量
  • 文章访问数:  2007
  • HTML全文浏览量:  691
  • PDF下载量:  344
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-06-21
  • 修回日期:  2022-09-04
  • 网络出版日期:  2024-01-12
  • 刊出日期:  2023-03-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭