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Polo-like Kinase 4:在治疗过程中的变化及其与儿童急性淋巴细胞白血病患者治疗反应和预后风险分层的关系。

Polo-like Kinase 4: the Variation During Therapy and its Relation to Treatment Response and Prognostic Risk Stratification in Childhood Acute Lymphoblastic Leukemia Patients.

机构信息

Department of Neonatology.

Department of Pediatrics, Handan Central Hospital, Handan China.

出版信息

J Pediatr Hematol Oncol. 2023 May 1;45(4):189-194. doi: 10.1097/MPH.0000000000002520. Epub 2022 Aug 11.

Abstract

Polo-like kinase 4 (PLK4) plays an essential role in the tumorigenesis of some blood malignancies; consequently, we hypothesized that PLK4 might serve as a potential biomarker in childhood acute lymphoblastic leukemia (ALL) patients. Therefore, this study investigated the expression of PLK4 and its clinical relevance in childhood ALL patients. Bone marrow specimens were collected from 95 childhood ALL patients and 20 primary immune thrombocytopenia patients (as controls), and their PLK4 expression (reverse transcription-quantitative polymerase chain reaction) was measured after enrollment. Besides, the PLK4 expression in childhood ALL patients was also determined at day 15 after the initiation of induction therapy (D15). PLK4 was increased in childhood ALL patients compared with controls (2.830 (interquartile range (IQR): 1.890-3.660) versus 0.976 (IQR: 0.670-1.288), P ≤0.001). PLK4 at diagnosis was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients ( P =0.027). Besides, PLK4 at diagnosis was positively linked with the Chinese Medical Association risk stratification ( P =0.016), but not with prednisone response ( P =0.077) or bone marrow response ( P =0.083). In addition, PLK4 was decreased at D15 after treatment compared with at diagnosis ( P ≤0.001). Interestingly, PLK4 at D15 (P=0.033) was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients. Furthermore, increased PLK4 at D15 was associated with poor prednisone response ( P =0.018), poor bone marrow response ( P =0.034), and increased the Chinese Medical Association risk stratification ( P =0.015). In terms of prognosis, high PLK4 was associated with shorter event-free survival ( P =0.020), whereas it was not related to the overall survival ( P =0.135). In conclusion, PLK4 has the potential as a biomarker for treatment response and prognostic risk stratification of childhood ALL patients.

摘要

丝氨酸/苏氨酸激酶 4(PLK4)在一些血液恶性肿瘤的发生中起着重要作用;因此,我们假设 PLK4 可能是儿童急性淋巴细胞白血病(ALL)患者的潜在生物标志物。因此,本研究调查了 PLK4 在儿童 ALL 患者中的表达及其临床相关性。采集了 95 例儿童 ALL 患者和 20 例原发性免疫性血小板减少症患者(作为对照)的骨髓标本,并在入组后测量其 PLK4 表达(逆转录-定量聚合酶链反应)。此外,还在诱导治疗开始后第 15 天(D15)测定了儿童 ALL 患者的 PLK4 表达。与对照组相比,儿童 ALL 患者的 PLK4 表达增加(2.830(四分位距(IQR):1.890-3.660)与 0.976(IQR:0.670-1.288),P ≤0.001)。T 细胞急性淋巴细胞白血病患者的 PLK4 在诊断时高于 B 细胞急性淋巴细胞白血病患者(P=0.027)。此外,PLK4 在诊断时与中国医师协会风险分层呈正相关(P=0.016),但与泼尼松反应(P=0.077)或骨髓反应(P=0.083)无关。此外,与诊断时相比,治疗后第 15 天(D15)的 PLK4 降低(P ≤0.001)。有趣的是,与 B 细胞急性淋巴细胞白血病患者相比,T 细胞急性淋巴细胞白血病患者的 D15 时的 PLK4 升高(P=0.033)。此外,D15 时升高的 PLK4 与泼尼松反应不良(P=0.018)、骨髓反应不良(P=0.034)和中国医师协会风险分层增加(P=0.015)相关。在预后方面,高 PLK4 与无事件生存时间较短相关(P=0.020),但与总生存时间无关(P=0.135)。总之,PLK4 有可能成为儿童 ALL 患者治疗反应和预后风险分层的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a964/10115493/9017493a9a23/mph-45-0189-g001.jpg

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