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Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia

BACKGROUND: 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 surv...

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Autores principales: Wang, Guiran, Yan, Guiling, Sang, Kanru, Yang, Huijie, Sun, Ni, Bai, Yuanyuan, Xu, Feng, Zheng, Xiaoqun, Chen, Zhanguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059359/
https://www.ncbi.nlm.nih.gov/pubmed/35501730
http://dx.doi.org/10.1186/s12885-022-09621-1
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author Wang, Guiran
Yan, Guiling
Sang, Kanru
Yang, Huijie
Sun, Ni
Bai, Yuanyuan
Xu, Feng
Zheng, Xiaoqun
Chen, Zhanguo
author_facet Wang, Guiran
Yan, Guiling
Sang, Kanru
Yang, Huijie
Sun, Ni
Bai, Yuanyuan
Xu, Feng
Zheng, Xiaoqun
Chen, Zhanguo
author_sort Wang, Guiran
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09621-1.
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spelling pubmed-90593592022-05-03 Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia Wang, Guiran Yan, Guiling Sang, Kanru Yang, Huijie Sun, Ni Bai, Yuanyuan Xu, Feng Zheng, Xiaoqun Chen, Zhanguo BMC Cancer Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09621-1. BioMed Central 2022-05-02 /pmc/articles/PMC9059359/ /pubmed/35501730 http://dx.doi.org/10.1186/s12885-022-09621-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Guiran
Yan, Guiling
Sang, Kanru
Yang, Huijie
Sun, Ni
Bai, Yuanyuan
Xu, Feng
Zheng, Xiaoqun
Chen, Zhanguo
Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
title Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
title_full Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
title_fullStr Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
title_full_unstemmed Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
title_short Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
title_sort circulating lnc-loc as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059359/
https://www.ncbi.nlm.nih.gov/pubmed/35501730
http://dx.doi.org/10.1186/s12885-022-09621-1
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