循环肿瘤DNA在血液系统恶性肿瘤中的研究进展

doi:10.3969/j.issn.1004-583X.2026.03.015

摘要/Abstract

摘要：

液体活检技术尤其是循环肿瘤DNA (circulating tumor DNA, ctDNA)检测,凭借非侵入性或微创性优势,在肿瘤临床诊疗中备受关注。血液系统恶性肿瘤ctDNA浓度较高,且富含肿瘤特异性遗传与表观遗传学异常,是进行ctDNA动态监测的理想靶点。数字聚合酶链式反应、二代测序等检测技术的进步,显著提升了ctDNA检测的敏感度与特异度,使其在血液系统恶性肿瘤的早期诊断、预后评估、治疗反应监测和微小残留病检测等领域的应用潜力不断拓展。本文系统综述了ctDNA的生物学特征、检测技术及其在淋巴瘤、多发性骨髓瘤、白血病等主要血液系统恶性肿瘤中的研究进展,探讨当前面临的挑战与未来发展方向,为ctDNA在血液肿瘤临床实践中的规范化应用提供参考。

关键词: 血液肿瘤, 循环肿瘤 DNA, 液体活检, 微小残留病, 二代测序

中图分类号:

R733

孟巧, 程春丽. 循环肿瘤DNA在血液系统恶性肿瘤中的研究进展[J]. 临床荟萃, 2026, 41(3): 280-284.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.03.015

https://www.lchc.cn/CN/Y2026/V41/I3/280

图/表 2

参考文献 48

[1]	Ferrarini I, Rigo A, Visco C. The mitochondrial anti-apoptotic dependencies of hematologic malignancies: From disease biology to advances in precision medicine[J]. Haematologica, 2022, 107(4): 790-802. doi:10.3324/haematol.2021.280201. pmid: 35045693
[2]	Chen H, Liang J, Liu Z, et al. Intense 18F-FAPI-04 uptake in bone marrow metastasis from recurrent postoperative gastric cancer negative on 18F-FDG PET/CT[J]. Clin Nucl Med, 2025, 50(12): e692-e694.doi:10.1097/rlu.0000000000005787.
[3]	Li JY, Zuo LP, Xu J, et al. Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future[J]. Blood Rev, 2024, 68. doi:10.1016/j.blre.2024.101237.
[4]	Ossandon MR, Agrawal L, Bernhard EJ, et al. Circulating tumor DNA assays in clinical cancer research[J]. J Natl Cancer Inst, 2018, 110(9): 929-934. doi:10.1093/jnci/djy105. pmid: 29931312
[5]	Soscia R, Della Starza I, De Novi L A, et al. Circulating cell-free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre-analytical biases[J]. Hematol Oncol, 2023, 41(1): 50-60. doi:10.1002/hon.3087.
[6]	Vimalathas G, Hansen MH, Cedile O, et al. Monitoring ctDNA in aggressive B-cell lymphoma: A prospective correlative study of ctDNA kinetics and PET-CT metrics[J]. Blood Adv, 2025, 9(20): 5207-5218. doi:10.1182/bloodadvances.2025016752. pmid: 40758954
[7]	Qi Z, Li Y, Wang Z, et al. Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor-informed assay[J]. Cancer Med, 2023, 12(16): 16687-16696. doi:10.1002/cam4.6286.
[8]	Al-Showbaki L, Wilson B, Tamimi F, et al. Changes in circulating tumor DNA and outcomes in solid tumors treated with immune checkpoint inhibitors: A systematic review[J]. J Immunother Cancer, 2023, 11(2):e005854. doi:10.1136/jitc-2022-005854.
[9]	Hitchen N, Shahnam A, Tie J. Circulating tumor DNA: A pan-cancer biomarker in solid tumors with prognostic and predictive value[J]. Annu Rev Med, 2025, 76(1): 207-223. doi:10.1146/annurev-med-100223-090016. pmid: 39570664
[10]	Cristiano S, Leal A, Phallen J, et al. Genome-wide cell-free DNA fragmentation in patients with cancer[J]. Nature, 2019, 570(7761): 385-389. doi:10.1038/s41586-019-1272-6.
[11]	Foda ZH, Annapragada AV, Boyapati K, et al. Detecting liver cancer using cell-free DNA fragmentomes[J]. Cancer Discov, 2023, 13(3): 616-631. doi:10.1158/2159-8290.CD-22-0659.
[12]	Hohaus S, Giachelia M, Massini G, et al. Cell-free circulating DNA in Hodgkin's and non-Hodgkin's lymphomas[J]. Ann Oncol, 2009, 20(8): 1408-1413. doi:10.1093/annonc/mdp006. pmid: 19465421
[13]	Abramson DH, Mandelker DL, Brannon AR, et al. Mutant-RB1 circulating tumor DNA in the blood of unilateral retinoblastoma patients: What happens during enucleation surgery: A pilot study[J]. PLoS One, 2023, 18(2): e0271505. doi:10.1371/journal.pone.0271505.
[14]	Malentacchi F, Pizzamiglio S, Verderio P, et al. Influence of storage conditions and extraction methods on the quantity and quality of circulating cell-free DNA (ccfDNA): The SPIDIA-DNAplas external quality assessment experience[J]. Clin Chem Lab Med, 2015, 53(12): 1935-1942. doi:10.1515/cclm-2014-1161. pmid: 25883202
[15]	Rong N, Chen K, Shao J, et al. A 3D scalable chamber-array chip for digital LAMP[J]. Anal Chem, 2023, 95(20): 7830-7838. doi:10.1021/acs.analchem.2c05288.
[16]	Lu Y, Li Z, Lim EH, et al. Digital PCR for minimal residual disease quantitation using immunoglobulin/T-cell receptor gene rearrangements in acute lymphoblastic leukemia: A proposed analytic algorithm[J]. J Mol Diagn, 2022, 24(6): 655-665. doi:10.1016/j.jmoldx.2022.03.004.
[17]	Qiang W, Jin L, Luo T, et al. Cell-free DNA chromosome copy number variations predict outcomes in plasma cell myeloma[J]. Blood Cancer J, 2023, 13(1): 136. doi:10.1038/s41408-023-00904-9. pmid: 37669974
[18]	Iams WT, Mackay M, Ben-Shachar R, et al. Concurrent tissue and circulating tumor DNA molecular profiling to detect guideline-based targeted mutations in a multicancer cohort[J]. JAMA Netw Open, 2024, 7(1): e2351700. doi:10.1001/jamanetworkopen.2023.51700. pmid: 38252441
[19]	Borea R, Saldanha EF, Maheswaran S, et al. Cancer in a drop: Advances in liquid biopsy in 2024[J]. Crit Rev Oncol Hematol, 2025, 213: 104776. doi:10.1016/j.critrevonc.2025.104776.
[20]	Roschewski M, Kurtz DM, Westin JR, et al. Remission assessment by circulating tumor DNA in large B-cell lymphoma[J]. J Clin Oncol, 2025, 43(34): 3652-3661. doi:10.1200/jco-25-01534.
[21]	Kurtz DM, Scherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma[J]. J Clin Oncol, 2018, 36(28): 2845-2853. doi:10.1200/jco.2018.78.5246. pmid: 30125215
[22]	Meriranta L, Alkodsi A, Pasanen A, et al. Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma[J]. Blood, 2022, 139(12): 1863-1877. doi:10.1182/blood.2021012852.
[23]	Spina V, Bruscaggin A, Cuccaro A, et al. Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma[J]. Blood, 2018, 131(22): 2413-2425. doi:10.1182/blood-2017-11-812073. pmid: 29449275
[24]	Calabretta E, Di Trani M, Corrado F, et al. Baseline circulating tumour DNA and interim PET predict response in relapsed/refractory classical Hodgkin lymphoma[J]. Br J Haematol, 2024, 204(2): 514-524. doi:10.1111/bjh.19162.
[25]	Nagy Á, Bátai B, Kiss L, et al. Parallel testing of liquid biopsy (ctDNA) and tissue biopsy samples reveals a higher frequency of EZH2 mutations in follicular lymphoma[J]. J Intern Med, 2023, 294(3): 295-313. doi:10.1111/joim.13674. pmid: 37259686
[26]	Lakhotia R, Melani C, Dunleavy K, et al. Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma[J]. Blood Adv, 2022, 6(8): 2667-2680. doi: 10.1182/bloodadvances.2021006397. pmid: 35143622
[27]	Gao Y, He H, Li X, et al. Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): A phase Ib/II study[J]. Signal Transduct Target Ther, 2024, 9(1): 121. doi:10.1038/s41392-024-01825-0.
[28]	Anderson KC, Auclair D, Adam SJ, et al. Minimal residual disease in myeloma: Application for clinical care and new drug registration[J]. Clin Cancer Res, 2021, 27(19): 5195-5212. doi:10.1158/1078-0432.Ccr-21-1059. pmid: 34321279
[29]	Hosoya H, Carleton M, Tanaka K, et al. Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma[J]. Nat Commun, 2025, 16(1): 1824. doi:10.1038/s41467-025-56486-6.
[30]	Chen R, Jin C, Liu K, et al. Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells[J]. Chin Med J (Engl), 2024, 138(19): 2481-2490. doi:10.1097/CM9.0000000000003306.
[31]	Biancon G, Gimondi S, Vendramin A, et al. Noninvasive molecular monitoring in multiple myeloma patients using cell-free tumor DNA: A pilot study[J]. J Mol Diagn, 2018, 20(6): 859-870. doi: 10.1016/j.jmoldx.2018.07.006. pmid: 30165206
[32]	Wachter F, Pikman Y. Pathophysiology of acute myeloid leukemia[J]. Acta Haematol, 2024, 147(2): 229-246. doi:10.1159/000536152.
[33]	Estey E, Hasserjian RP, Dohner H. Distinguishing AML from MDS: A fixed blast percentage may no longer be optimal[J]. Blood, 2022, 139(3): 323-332. doi:10.1182/blood.2021011304.
[34]	Hisamatsu Y, Ando K, Kudo K, et al. A 14-gene panel for predicting colorectal cancer recurrence using circulating tumor DNA in different testing conditions[J]. Cancer Sci, 2025, 116(9): 2499-2506. doi:10.1111/cas.70114.
[35]	Manabe M, Inano N, Hagiwara Y, et al. Anisolymphocytosis: A clue for Richter transformation[J]. Clin Case Rep, 2024, 12(5): e8639. doi:10.1002/ccr3.8639.
[36]	Skorka K, Chojnacki M, Masternak M, et al. The predominant prognostic significance of NOTCH1 mutation defined by emulsion PCR in chronic lymphocytic leukemia[J]. Cancer Manag Res, 2021, 13: 3663-3674. doi:10.2147/cmar.S302245.
[37]	Kang Q, Henry NL, Paoletti C, et al. Comparative analysis of circulating tumor DNA stability in K₃EDTA, Streck, and CellSave blood collection tubes[J]. Clin Biochem, 2016, 49(18): 1354-1360. doi:10.1016/j.clinbiochem.2016.03.012.
[38]	Cohen SA, Liu MC, Aleshin A. Practical recommendations for using ctDNA in clinical decision making[J]. Nature, 2023, 619(7969): 259-268. doi:10.1038/s41586-023-06225-y.
[39]	Chen J, Gale RP, Hu Y, et al. Measurable residual disease (MRD)-testing in haematological and solid cancers[J]. Leukemia, 2024, 38(6): 1202-1212. doi:10.1038/s41375-024-02252-4. pmid: 38637690
[40]	Dang DK, Park BH. Circulating tumor DNA: Current challenges for clinical utility[J]. J Clin Invest, 2022, 132(12):e154941. doi:10.1172/JCI154941.
[41]	Huang C, Hu S, Zhang X, et al. Sensitive and selective ctDNA detection based on functionalized black phosphorus nanosheets[J]. Biosens Bioelectron, 2020, 165: 112384. doi:10.1016/j.bios.2020.112384.
[42]	Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: A report from the ESMO Precision Medicine Working Group[J]. Ann Oncol, 2022, 33(8): 750-768. doi:10.1016/j.annonc.2022.05.520. pmid: 35809752
[43]	Lin C, Liu X, Zheng B, et al. Liquid biopsy, ctDNA diagnosis through NGS[J]. Life (Basel), 2021, 11(9):890. doi:10.3390/life11090890.
[44]	Murtaza M, Dawson SJ, Tsui DW, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA[J]. Nature, 2013, 497(7447): 108-112. doi:10.1038/nature12065.
[45]	Moding EJ, Nabet BY, Alizadeh AA, et al. Detecting liquid remnants of solid tumors: Circulating tumor DNA minimal residual disease[J]. Cancer Discov, 2021, 11(12): 2968-2986. doi:10.1158/2159-8290.Cd-21-0634. pmid: 34785539
[46]	Zhang JX, Yordanov B, Gaunt A, et al. A deep learning model for predicting next-generation sequencing depth from DNA sequence[J]. Nat Commun, 2021, 12(1): 4387. doi:10.1038/s41467-021-24497-8. pmid: 34282137
[47]	Bahado-Singh R, Vlachos KT, Aydas B, et al. Precision oncology: Artificial intelligence and DNA methylation analysis of circulating cell-free DNA for lung cancer detection[J]. Front Oncol, 2022, 12: 790645. doi:10.3389/fonc.2022.790645.
[48]	Markus H, Chandrananda D, Moore E, et al. Refined characterization of circulating tumor DNA through biological feature integration[J]. Sci Rep, 2022, 12(1): 1928. doi:10.1038/s41598-022-05606-z.

检测技术	敏感度	特异度	检测范围	优势	局限性	适用场景
微滴式dPCR	0.001%~0.01%	95%~99%	已知突变位点	操作简便、成本低	仅检测已知突变	MRD监测、耐药突变检测
珠基乳液扩增与磁珠分选数字聚合酶链式反应	0.001%~0.01%	96%~99%	多个已知突变位点	可同时检测多靶点	通量较低	多突变位点联合检测
癌症个体化深度测序	0.0001%~0.001%	97.0%~99.5%	靶向基因 Panel	高敏感度、高特异度	依赖探针设计	全景式分子分型、MRD 监测
Ig基因重排测序	0.001%~0.01%	98.0%~99.5%	Ig基因重排	针对B细胞肿瘤特异性强	仅适用于B细胞肿瘤	B细胞淋巴瘤、MM的MRD检测
全基因组/全外显子组测序	0.1%~1%	90%~95%	全基因组/全外显子组	检测所有类型变异	成本高、数据量大	发现新突变、拷贝数变异分析
甲基化NGS	0.01%~0.1%	94%~98%	甲基化位点	区分肿瘤与正常组织来源	数据分析复杂	分子分型、预后评估

检测技术	敏感度	特异度	检测范围	优势	局限性	适用场景
微滴式dPCR	0.001%~0.01%	95%~99%	已知突变位点	操作简便、成本低	仅检测已知突变	MRD监测、耐药突变检测
珠基乳液扩增与磁珠分选数字聚合酶链式反应	0.001%~0.01%	96%~99%	多个已知突变位点	可同时检测多靶点	通量较低	多突变位点联合检测
癌症个体化深度测序	0.0001%~0.001%	97.0%~99.5%	靶向基因 Panel	高敏感度、高特异度	依赖探针设计	全景式分子分型、MRD 监测
Ig基因重排测序	0.001%~0.01%	98.0%~99.5%	Ig基因重排	针对B细胞肿瘤特异性强	仅适用于B细胞肿瘤	B细胞淋巴瘤、MM的MRD检测
全基因组/全外显子组测序	0.1%~1%	90%~95%	全基因组/全外显子组	检测所有类型变异	成本高、数据量大	发现新突变、拷贝数变异分析
甲基化NGS	0.01%~0.1%	94%~98%	甲基化位点	区分肿瘤与正常组织来源	数据分析复杂	分子分型、预后评估

肿瘤类型	核心应用场景	关键分子标志物/技术	临床价值
淋巴瘤
弥漫大B细胞淋巴瘤	分子分型、预后评估、MRD监测	MYD88/CD79B/EZH2 突变、癌症个体化深度测序	早期预测治疗反应、复发预警(提前 4~6 个月)
经典霍奇金淋巴瘤	肿瘤负荷评估、MRD 监测	STAT6/GNA13/SOCS1 突变、相位变异富集检测测序	补充正电子发射断层显像/计算机断层扫描提升 MRD 敏感度
滤泡淋巴瘤	MRD 监测、组织学转化预警	EZH2/CREBBP突变、Ig重排	动态评估惰性淋巴瘤进展风险
套细胞淋巴瘤	疗效预测、耐药监测	CCND1-IGH融合、ATM突变	指导靶向治疗方案调整
结外NK/T 细胞淋巴瘤	诊断、预后评估	甲基化谱、爱泼斯坦-巴尔病毒相关突变	解决诊断标志物缺乏问题
MM	肿瘤负荷评估、MRD 监测、髓外复发监测	Ig 重排、拷贝数变异、TP53 突变	无创替代骨髓活检、监测髓外复发
白血病
AML	分子分型、MRD 监测	NPM1/IDH1/2/FLT3 突变、5hmC签名	动态评估克隆进化、早期复发预警
急性淋巴细胞白血病	MRD 监测、中枢神经系统侵犯评估	BCR-ABL1融合、IKZF1缺失	评估髓外病变风险
慢性淋巴细胞白血病	疾病进展评估、Richter 转化预警	IGHV/TP53/SF3B1突变	区分惰性与进展性急性淋巴细胞白血病

肿瘤类型	核心应用场景	关键分子标志物/技术	临床价值
淋巴瘤
弥漫大B细胞淋巴瘤	分子分型、预后评估、MRD监测	MYD88/CD79B/EZH2 突变、癌症个体化深度测序	早期预测治疗反应、复发预警(提前 4~6 个月)
经典霍奇金淋巴瘤	肿瘤负荷评估、MRD 监测	STAT6/GNA13/SOCS1 突变、相位变异富集检测测序	补充正电子发射断层显像/计算机断层扫描提升 MRD 敏感度
滤泡淋巴瘤	MRD 监测、组织学转化预警	EZH2/CREBBP突变、Ig重排	动态评估惰性淋巴瘤进展风险
套细胞淋巴瘤	疗效预测、耐药监测	CCND1-IGH融合、ATM突变	指导靶向治疗方案调整
结外NK/T 细胞淋巴瘤	诊断、预后评估	甲基化谱、爱泼斯坦-巴尔病毒相关突变	解决诊断标志物缺乏问题
MM	肿瘤负荷评估、MRD 监测、髓外复发监测	Ig 重排、拷贝数变异、TP53 突变	无创替代骨髓活检、监测髓外复发
白血病
AML	分子分型、MRD 监测	NPM1/IDH1/2/FLT3 突变、5hmC签名	动态评估克隆进化、早期复发预警
急性淋巴细胞白血病	MRD 监测、中枢神经系统侵犯评估	BCR-ABL1融合、IKZF1缺失	评估髓外病变风险
慢性淋巴细胞白血病	疾病进展评估、Richter 转化预警	IGHV/TP53/SF3B1突变	区分惰性与进展性急性淋巴细胞白血病

循环肿瘤DNA在血液系统恶性肿瘤中的研究进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 48

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王嗣欣, 余群, 何嘉盛. EB病毒致急性小脑炎1例并文献复习[J]. 临床荟萃, 2026, 41(1): 57-59.
[2]	陈文江, 舒展, 周来显. 基于核酸适配体的肺癌诊断和治疗研究进展[J]. 临床荟萃, 2025, 40(8): 742-747.
[3]	滕怀千, 萧俊, 肖龙敏, 王安琪. 小儿肿瘤中ctDNA的研究进展[J]. 临床荟萃, 2025, 40(8): 764-768.
[4]	赵雅静, 陶千山, 沈元元, 董毅. 地西他滨维持治疗对适合强化疗中低危急性髓细胞白血病患者生存的影响[J]. 临床荟萃, 2025, 40(5): 439-444.
[5]	陈绍鹏, 张华平. 液体活检在胶质母细胞瘤诊断与监测中的研究进展[J]. 临床荟萃, 2025, 40(12): 1147-1152.
[6]	范桥珍, 康蕊, 张婷. 多参数流式细胞术识别与急性髓系白血病微小残留病具有类似表型的再生细胞[J]. 临床荟萃, 2024, 39(8): 716-727.
[7]	刘婉琦, 樊树芹, 庄瑞雪, 贺峰, 刘振川, 解忠祥. 成人水痘-带状疱疹病毒相关颅内感染5例临床分析[J]. 临床荟萃, 2024, 39(2): 149-154.
[8]	黄赛虎, 龙中洁, 董兴强, 孟祥营, 吴水燕, 柏振江. 血液肿瘤患儿合并脓毒血症的病原学特点及临床特征[J]. 临床荟萃, 2024, 39(1): 38-42.
[9]	沃拉孜汗·玛德尼亚提, 迪力夏提·图尔迪麦麦提, 李梦晨, 拜合提尼沙·吐尔地. 宏基因组二代测序技术在肺结核诊断中应用价值的meta分析[J]. 临床荟萃, 2023, 38(5): 389-398.
[10]	高梦鸽，常英军，赵晓甦. 循环肿瘤DNA在淋巴瘤微小残留病检测中的应用[J]. 临床荟萃, 2019, 34(5): 467-471.
[11]	王玮. 从遗传的角度谈罕见病的诊治进展[J]. 临床荟萃, 2019, 34(3): 201-206.
[12]	杨锦才，李莉娟，郝正栋，郭晓嘉，楚松林，张连生. 靶向免疫负调控的药物在血液肿瘤中的应用及前景[J]. 临床荟萃, 2018, 33(8): 723-727.
[13]	苏文思1，袁娇娇1，陆滢2. 比较脐血与非血缘不全相合供者移植对恶性血液病疗效的Meta分析[J]. 临床荟萃, 2018, 33(3): 244-250.
[14]	任金海，郭晓楠. 2017年血液肿瘤研究进展[J]. 临床荟萃, 2018, 33(1): 40-45.
[15]	高欣宝，温树鹏，邢丽娜，牛志云，王颖，王福旭，张学军. 单倍型相合造血干细胞移植治疗恶性血液病与人类白细胞抗原相合同胞移植疗效相当[J]. 临床荟萃, 2017, 32(8): 665-671.