Abstract
// Ji Zhang 1, 2 , Yawen Jiang 1 , Xu Han 1 , Wenen Liu 3 , Xielan Zhao 4 and Jing Liu 1 1 Molecular Biology Research Center, School of Life Sciences, Central South University, Changsha 410078, China 2 Department of Hematology, The First Affiliated Hospital, University of South China, Hengyang 421001, China 3 Department of Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, 410008, China 4 Department of Hematology, Xiangya Hospital of Central South University, Changsha, 410008, China Correspondence to: Jing Liu, email: jingliucsu@hotmail.com, liujing2@sklmg.edu.cn Ji Zhang, email: zhang_ji001@hotmail.com Keywords: plasma miRNA; chronic myeloid leukemia; expression profile; biological function; miR-451a Received: September 13, 2017 Accepted: November 16, 2017 Published: January 02, 2018 ABSTRACT microRNAs play important regulatory roles in hematologic malignancies, and dysregulation of circulating miRNAs serves as diagnostic, prognostic and predictive biomarkers in many diseases. The correlation of plasma miRNA profiles with the progression of chronic myeloid leukemia (CML) has not been investigated. We have applied microarrays to identify differentially expressed miRNAs, followed by qRT-PCR to validate candidate miRNAs from four sample pools including chronic phase (CP), accelerated phase(AP), blast crisis(BC) and healthy control. Clustering analyses revealed varying phase-specific patterns of plasma miRNA expression during CML progression. Different phases of CML showed differential expression profiles between sample pools during the progression. The functional annotation tool, DAVID, found that putative targets of dysregulated miRNAs in different phases of diease are involved in several important signaling pathways. Gradually decreased expression levels of miR-451a were validated in CML patients from the CP to AP and BC; when CML patients achieved major molecular response (MMR), miR-451a expression was increased and restored to normal range. These data provide an important resource for studies on CML progression and allow a better understanding of the fundamental differences in plasma miRNA expression profiles among the different phases of CML.
Highlights
Chronic myeloid leukemia (CML) is a kind of hematopoietic malignancy characterized by a reciprocal chromosomal translocation, t(9;22)(q34;q11), known as the Philadelphia (Ph) chromosome, producing the BcrAbl oncogene [1, 2]
Decreased expression levels of miR-451a were validated in chronic myeloid leukemia (CML) patients from the chronic phase (CP) to accelerated phase (AP) and blast crisis (BC); when CML patients achieved major molecular response (MMR), miR-451a expression was increased and restored to normal range
To further examine the possible roles of miRNAs in CML patients, we investigated plasma miRNA expression profiles at different stages of CML, which may shed light on the mechanisms involved in the progression of CML
Summary
Chronic myeloid leukemia (CML) is a kind of hematopoietic malignancy characterized by a reciprocal chromosomal translocation, t(9;22)(q34;q11), known as the Philadelphia (Ph) chromosome, producing the BcrAbl oncogene [1, 2]. CML is a multiphase disease with the phases include chronic phase (CP), accelerated phase (AP) and blast phase, known as blast crisis (BC), and can be diagnosed in each of the three distinct phases. MiRNAs can negatively regulate gene expression through partial base-pairing with the 3’-untranslated region of their target mRNAs, and they inhibit the translation and/ or lead to degradation of these mRNAs. Recently, more attention has been paid on the roles of circulating miRNAs in physiological and pathological processes. More attention has been paid on the roles of circulating miRNAs in physiological and pathological processes These circulating miRNAs are stable and can be protected from degradation by encapsulation in lipid vesicles including microvesicles, exosomes, and apoptotic bodies. Circulating miRNAs have a regulatory role in www.impactjournals.com/oncotarget s469
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