人 Kruppel 样因子 3 在周围血液中的表达作为急性白血病有前途的生物标志物。

Expression of human Krüppel-like factor 3 in peripheral blood as a promising biomarker for acute leukemia.

机构信息

Department of Hematology, Peking University First Hospital, Beijing, China.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, China.

出版信息

Cancer Med. 2020 Apr;9(8):2803-2811. doi: 10.1002/cam4.2911. Epub 2020 Feb 26.

DOI:10.1002/cam4.2911

PMID:32101374

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7163096/

Abstract

BACKGROUND

Universal gene targets are in persistent demand by real-time quantitative polymerase chain reaction (RT-qPCR)-based methods in acute leukemia (AL) diagnosis and monitoring. Human Krüppel-like factor 3 (hKLF3), a newly cloned human transcription factor, has proved to be a regulator of hematopoiesis.

METHODS

Sanger sequencing was performed in bone marrow (BM) samples from 17 AL patients for mutations in hKLF3 coding exons. hKLF3 expression in peripheral blood (PB) and BM samples from 45 AL patients was dynamically detected by RT-qPCR. PB samples from 31 healthy donors were tested as normal controls.

RESULTS

No mutation was sequenced in hKLF3 coding exons. hKLF3 expression in PB of AL was significantly lower than that in healthy donors [0.30 (0.02-1.07) vs 1.18 (0.62-3.37), P < .0001]. Primary acute myeloid leukemia (AML) exhibited the least expression values compared with secondary AML and acute lymphoblastic leukemia. Receiver operating characteristic (ROC) analyses suggested that hKLF3 expression in PB was a good marker for AML diagnosis with an AUC of 0.99 (95% CI 0.98-1.00) and an optimum cutoff value of 0.67 (sensitivity 93.94% and specificity 93.55%). hKLF3 expression was upregulated significantly when AML patients acquired morphological complete remission (CR), and the level of hKLF3 seemed to be higher in patients with deeper CR than in patients with minimal residual disease (MRD). Paired PB and BM samples showed highly consistent alteration in hKLF3 expression (r = .6533, P = .001). Besides, a significantly converse correlation between decreased hKLF3 expression in PB and markers for leukemic load was observed.

CONCLUSIONS

hKLF3 expression in PB may act as a potential marker for AL diagnosis and monitoring.

摘要

背景

实时定量聚合酶链反应（RT-qPCR）方法在急性白血病（AL）的诊断和监测中一直需要通用的基因靶点。人类 Kruppel 样因子 3（hKLF3）是一种新克隆的人类转录因子，已被证明是造血的调节剂。

方法

对 17 例 AL 患者的骨髓（BM）样本进行 Sanger 测序，以检测 hKLF3 编码外显子的突变。通过 RT-qPCR 动态检测 45 例 AL 患者外周血（PB）和 BM 样本中的 hKLF3 表达。以 31 例健康供者的 PB 样本作为正常对照进行检测。

结果

hKLF3 编码外显子未测序到突变。AL 患者的 PB 中 hKLF3 表达明显低于健康供者[0.30（0.02-1.07）比 1.18（0.62-3.37），P<0.0001]。原发性急性髓系白血病（AML）与继发性 AML 和急性淋巴细胞白血病相比，表达值最低。受试者工作特征（ROC）分析表明，PB 中 hKLF3 表达是 AML 诊断的良好标志物，AUC 为 0.99（95%CI 0.98-1.00），最佳截断值为 0.67（敏感性 93.94%，特异性 93.55%）。当 AML 患者获得形态学完全缓解（CR）时，hKLF3 表达显著上调，且深度 CR 患者的 hKLF3 水平似乎高于微小残留病（MRD）患者。配对 PB 和 BM 样本显示 hKLF3 表达高度一致（r=0.6533，P=0.001）。此外，还观察到 PB 中 hKLF3 表达降低与白血病负荷标志物呈显著负相关。