MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis.

This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms. METHODS: Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance. RESULTS: BMSCs-derived exosomes effectively suppressed cell proliferation (both P 
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research

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midt-Arras Fms-like tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinases (RTK) and is involved in cell survival, proliferation, and differentiation of haematopoietic progenitors of lymphoid and myeloid lineages. Oncogenic mutations in the FLT3 gene resulting in constitutively active FLT3 variants are frequently found in acute myeloid leukaemia (AML) patients and correlate with patient’s poor survival. Targeting FLT3 mutant leukaemic stem cells (LSC) is a key to efficient treatment of patients with relapsed/refractory AML. It is therefore essential to understand how LSC escape curren...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations. AbstractTo explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next ‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction che...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
ong The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling path...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In this study, we evaluated the prognostic significance of CLIC4 expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis and multi-omics analysis with weighted correlation network analysis (WGCNA) in the CN-AML group were also presented. Based on CLIC4 and its related genes, microRNA–target gene interaction network analysis and downstream gene ontology analysis were performed to unveil the complex functions behind CLIC4.Results: We demonstrated that the overexpression of CLIC4 was notably associated with unfavorable outcome in the two independent cohorts ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
elosi Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors. In the last years, there has been a dramatic improvement in the understanding of the molecular alterations driving cellular signaling and biochemical changes determining the survival advantage, stimulation of proliferation, and impairment of cellular differentiation of leukemic cells. These molecular alterations influence clinical outcomes and provide potential targets for drug development...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Ring finger proteins contain a characteristic ring finger motif and perform a wide range of biological functions in living organisms. These genes are abnormally expressed in many cancers. We found that the expression level of Ring finger protein 220 (RNF220) was negatively correlated with the disease-free survival (DFS) and overall survival (OS) of acute myeloid leukaemia (AML) patients. Moreover, the mRNA level of this gene is significantly higher in the bone marrow cells of AML patients than in the mobilized peripheral blood haematopoietic stem cells of healthy donors. The overexpression of RNF220 promo...
Source: Blood Cells, Molecules and Diseases - Category: Hematology Authors: Tags: Blood Cells Mol Dis Source Type: research
Abstract The tumor suppressor p53 exerts pivotal roles in hematopoietic stem cell (HSC) homeostasis. Mutations of the TP53 gene have recently been described in individuals with clonal hematopoieis conferring substantial risk of developing blood cancers. In patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), TP53 aberrations - mutations, deletions and a combination thereof - are encountered at a constant frequency of approximately 10%. These aberrations affect HSCs transforming them into preleukemic stem cells, pinpointing their central role in leukemogenesis. AML and MDS with TP53 aberr...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Kobbe Thomas Schroeder To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionWe demonstrated that MDSC ‐like blasts drive AML‐specific immune‐escape mechanisms by suppressing T cell proliferation and restoring T cell‐suppressed NB4 cell proliferation, with clinically higher fractions of MDSC‐like blasts at diagnosis resulting in poor prognosis.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
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