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肾母细胞瘤基因定量分析与多参数流式细胞术联合用于异基因造血干细胞移植后急性髓系白血病患者微小残留病监测

Combined usage of Wilms' tumor gene quantitative analysis and multiparameter flow cytometry for minimal residual disease monitoring of acute myeloid leukemia patients after allogeneic hematopoietic stem cells transplantation.

作者信息

Hao Yingchan, Cheng Yanhong, Wu Quan, Zhang Aimei, Jiang Xiaoxiao, Xu Xiucai

机构信息

Central Laboratory, The Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.

出版信息

Exp Ther Med. 2018 Feb;15(2):1403-1409. doi: 10.3892/etm.2017.5547. Epub 2017 Nov 23.

DOI:10.3892/etm.2017.5547
PMID:29434724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5774438/
Abstract

High expression of the Wilms' tumor gene (WT1) in acute myeloid leukemia (AML) has been considered as a sensitive marker of minimal residual disease (MRD). The present study investigated the significance of quantitative analysis of WT1 mRNA, combined with multiparameter flow cytometry (MFC) regarding its efficacy and prognostic as well as relapse prediction value for leukemia patients with hematopoietic stem cell transplantation. Reverse-transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in the initial and relapse group was significant higher than that in the complete remission (CR) group (P<0.01). WT1 and the donor chimerism were negatively correlated (r=-0.73, P<0.05). In all AML patients, WT1 was the highest in the M3 subtype and the lowest in the M1 subtype. Follow-up of 12 AML patients demonstrated that WT1 gene expression levels markedly decreased after CR, but obviously increased after relapse, as did the rate of the leukemia cells detected by MFC. The combined usage of MFC and WT1 monitoring contributed to an improved detection rate of relapse (91.7%), and may be used to monitor MRD, assess the treatment efficacy and prognosis, and predict the risk of recurrence in leukemia patients without specific molecular markers after allogeneic hematopoietic stem cell transplantation.

摘要

肾母细胞瘤基因(WT1)在急性髓系白血病(AML)中的高表达被认为是微小残留病(MRD)的敏感标志物。本研究探讨了WT1 mRNA定量分析联合多参数流式细胞术(MFC)对接受造血干细胞移植的白血病患者的疗效、预后及复发预测价值的意义。逆转录定量聚合酶链反应分析表明,初发组和复发组WT1的表达显著高于完全缓解(CR)组(P<0.01)。WT1与供体嵌合率呈负相关(r=-0.73,P<0.05)。在所有AML患者中,WT1在M3亚型中最高,在M1亚型中最低。对12例AML患者的随访表明,CR后WT1基因表达水平明显下降,但复发后明显升高,MFC检测的白血病细胞比例也是如此。MFC与WT1监测联合使用有助于提高复发检测率(91.7%),可用于监测MRD、评估治疗疗效和预后,以及预测异基因造血干细胞移植后无特定分子标志物的白血病患者的复发风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/7d125c60d2a4/etm-15-02-1403-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/a38c79c89d76/etm-15-02-1403-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/284c52ccfbd0/etm-15-02-1403-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/58499d2e505c/etm-15-02-1403-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/7d125c60d2a4/etm-15-02-1403-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/a38c79c89d76/etm-15-02-1403-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/284c52ccfbd0/etm-15-02-1403-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/58499d2e505c/etm-15-02-1403-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a971/5774438/7d125c60d2a4/etm-15-02-1403-g03.jpg

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本文引用的文献

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Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients.在核型正常的急性髓系白血病患者中,使用威尔姆斯瘤1基因表达作为预后和微小残留病监测的可靠标志物。
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Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients.
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