Purpose. To elucidate the microRNAs existent in exosomes derived from stored red blood cell (RBC) unit and their potential function. Materials and Methods. Exosomes were isolated from the supernatant derived from stored RBC units by sequential centrifugation. Isolated exosomes were characterized by TEM (transmission electron microscopy), western blotting, and DLS (dynamic light scattering). MicroRNA (miRNA) microarray was performed to detect the expression of miRNAs in 3 exosome samples. Results revealed miRNAs that were simultaneously expressed in the 3 exosome samples and were previously reported to exist in mature RBCs. Functions and potential pathways of some detected miRNAs were illustrated by bioinformatic analysis. Validation of the top 3 abundant miRNAs was carried out by qRT-PCR (quantitative reverse transcription‐polymerase chain reaction). Results. TEM and DLS revealed the mean size of the exosomes (RBC-derived) as 64.08 nm. These exosomes exhibited higher abundance of short RNA than the long RNA. 78 miRNAs were simultaneously detected in 3 exosome samples and mature RBCs. Several biological processes might be impacted by these miRNAs, through their target gene(s) enriched in a particular signalling pathway. The top 3 (abundant) miRNAs detected were as follows: miR-125b-5p, miR-4454, and miR-451a. qRT-PCR revealed higher abundance of miR-451a than others. Only miR-4454 and miR-451a abundance tended to increase with increasing storage time. Conclusion. Exosomes derived from stored RBC units possessed multiple miRNAs and, hence, could serve various functions. The function of exosomes (RBC-derived) might be implemented partly by the predominantly enriched miR-451a.
Chronic myeloid leukemia (CML) is relatively rare in children, with an average annual incidence of 0.6 to 1.0 case per million in children <15 years and 2.2 cases per million in adolescents aged 15 to 19 years, accounting for 2% to 3% and 9% of all newly diagnosed leukemia cases in these two age groups, respectively. [1] Imatinib mesylate (IM) was approved by the US Food and Drug Administration (FDA) in 2003 and has gradually replaced hematopoietic stem cell transplantation (HSCT) as the first-line treatment for pediatric patients with chronic-phase CML (CML-CP). [2] However, IM treatment is discontinued in 25% to 29% of pediatric patients with CML-CP because of drug resistance or intolerance. [3] For such patients, second-generation tyrosine kinase inhibitors (2G-TKIs), including dasatinib and nilotinib, were approved by the FDA as firstand second-line therapies in 2017 and 2018, respectively. [2] However, given the rarity of this neoplasm and the lack of clinical trial data, treatments for pediatric CML follow the recommended adult regimen, and little is known about the long-term efficacy and safety of these treatments in children and adolescents. [2] Furthermore, there are few reports detailing the sequential use of IM as first-line treatment followed by 2G-TKIs as second-line therapy in Chinese pediatric patients with CML. Therefore, there is a strong need to investigate the long-term effects of IM treatment in a large cohort of Chinese pediatric patients. In this report, we retrospectively analyzed the long-term follow-up results of 58 pediatric patients with CML-CP treated with IM as first-line therapy and 2G-TKIs as second-line therapy in a single South China center.Yong-Zhi Zheng and Jian Li contributed equally to this work.
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