Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, Zhejiang, 325000, P.R. China.
The First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, P.R. China.
BMC Cancer. 2022 May 2;22(1):481. doi: 10.1186/s12885-022-09621-1.
Acute promyelocytic leukaemia (APL) is a unique subtype of acute myeloid leukaemia (AML) characterized by haematopoietic failure caused by the accumulation of abnormal promyelocytic cells in bone marrow (BM). However, indispensable BM biopsy frequently afflicts patients in leukaemia surveillance, which increases the burden on patients and reduces compliance. This study aimed to explore whether the novel circulating long noncoding RNA LOC100506453 (lnc-LOC) could be a target in diagnosis, assess the treatment response and supervise the minimal residual disease (MRD) of APL, thereby blazing a trail in noninvasive lncRNA biomarkers of APL.
Our study comprised 100 patients (40 with APL and 60 with non-APL AML) and 60 healthy donors. BM and peripheral blood (PB) sample collection was accomplished from APL patients at diagnosis and postinduction. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate lnc-LOC expression. A receiver operating characteristic (ROC) analysis was implemented to analyse the value of lnc-LOC in the diagnosis of APL and treatment monitoring. For statistical analysis, the Mann-Whitney U test, a t test, and Spearman's rank correlation test were utilized.
Our results showed that BM lnc-LOC expression was significantly different between APL and healthy donors and non-APL AML. lnc-LOC was drastically downregulated in APL patients' BM after undergoing induction therapy. Lnc-LOC was upregulated in APL cell lines and downregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation, preliminarily verifying that lnc-LOC has the potential to be considered a treatment monitoring biomarker. PB lnc-LOC was positively correlated with BM lnc-LOC in APL patients, non-APL AML patients and healthy donors and decreased sharply after complete remission (CR). However, upregulated lnc-LOC was manifested in relapsed-refractory patients. A positive correlation was revealed between PB lnc-LOC and PML-RARα transcript levels in BM samples. Furthermore, we observed a positive correlation between PB lnc-LOC and BM lnc-LOC expression in APL patients, suggesting that lnc-LOC can be utilized as a noninvasive biomarker for MRD surveillance.
Our study demonstrated that PB lnc-LOC might serve as a novel noninvasive biomarker in the treatment surveillance of APL, and it innovated the investigation and application of newly found lncRNAs in APL noninvasive biomarkers used in diagnosis and detection.
急性早幼粒细胞白血病（APL）是一种独特的急性髓系白血病（AML）亚型，其特征是骨髓（BM）中异常早幼粒细胞的积累导致造血功能衰竭。然而，不可或缺的 BM 活检经常给白血病监测患者带来困扰，增加了患者的负担，降低了依从性。本研究旨在探讨新型循环长链非编码 RNA LOC100506453（lnc-LOC）是否可作为 APL 诊断、评估治疗反应和监测微小残留病（MRD）的靶点，从而为 APL 的无创 lncRNA 生物标志物开辟新途径。
本研究纳入 100 例患者（40 例 APL 和 60 例非 APL AML）和 60 名健康供者。APL 患者在诊断和诱导后采集 BM 和外周血（PB）样本。采用实时定量 PCR（qRT-PCR）检测 lnc-LOC 的表达。通过接受者操作特征（ROC）分析评估 lnc-LOC 在 APL 诊断和治疗监测中的价值。统计分析采用 Mann-Whitney U 检验、t 检验和 Spearman 秩相关检验。
本研究结果显示，APL 患者和健康供者及非 APL AML 患者的 BM lnc-LOC 表达存在显著差异。APL 患者接受诱导治疗后 BM 中的 lnc-LOC 表达明显下调。APL 细胞系中 lnc-LOC 表达上调，经全反式维甲酸（ATRA）诱导髓系分化后下调，初步验证 lnc-LOC 具有作为治疗监测生物标志物的潜力。APL 患者、非 APL AML 患者和健康供者的 PB lnc-LOC 与 BM lnc-LOC 呈正相关，完全缓解（CR）后急剧下降。然而，复发/难治性患者表现出上调的 lnc-LOC。此外，我们还发现 BM 样本中 PB lnc-LOC 与 PML-RARα 转录本水平呈正相关。进一步观察到 APL 患者 PB lnc-LOC 与 BM lnc-LOC 表达呈正相关，提示 lnc-LOC 可用作 MRD 监测的无创生物标志物。
本研究表明，PB lnc-LOC 可能作为 APL 治疗监测的新型无创生物标志物，为新发现的 lncRNA 在 APL 无创生物标志物的诊断和检测中的研究和应用提供了创新思路。
