Objective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. Results The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. Conclusion The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.

Apoptosis induction and differentiation of promyelocytic leukemic cells into mature cells are major strategies for the drug-based treatment of leukemia. Lidamycin (LDM) which is a member of the enediyne antibiotic family exhibits extreme cytotoxicity. In the present study, the induction of apoptosis and differentiation in human chronic myeloid leukemia K562 cells by low concentrations of lidamycin were investigated. K562 cells were treated with lidamycin at various concentrations for 48 h, and accumulated in the metaphase as determined in previous experiments. Cell viability was determined using a Cell Counting Kit-8 (CCK-8) assay and the IC 50 value of lidamycin was 0.1±3.2 nM. Induction of apoptosis was investigated morphologically by acridine orange/ethidium bromide (AO/EtBr) staining. Growth inhibition and apoptosis induction were observed in cells treated with low concentrations of lidamycin. In addition, western blot analysis revealed that treatment of the K562 cells with lidamycin at low concentrations upregulated the expression of caspase-8 and caspase-3. The induction of differentiation in human chronic myeloid leukemia K562 cells by lidamycin at low concentrations was also investigated. The nitroblue tetrazolium reduction ability of K562 cells was increased following treatment with lidamycin. Low concentrations of lidamycin triggered erythroid differentiation among K562 cells, indicated by morphological changes, increased hemoglobin content, and the expression of cell surface antigens such as CD71. Additionally the expression of GATA-binding factor 1 (GATA-1) protein in low concentration lidamycin-treated K562 cells was increased. The results of the present study suggest that a low-concentration lidamycin exerts effects on apoptosis and erythroid differentiation induction by increasing the expression of caspases and GATA-1 protein. Lidamycin may serve a positive role in relevant targeted chemotherapy and may represent a potential candidate for chronic myelogenous leukemia differentiation-inducing treatment.

Objectives: VAV family genes ( VAV1, VAV2, and VAV3) are associated with prognosis in various cancers; however, they have not been evaluated in acute myeloid leukemia (AML). In this study, the prognostic value of VAV expression in AML was evaluated by a single-center study in combination with bioinformatics analyses. Methods: The expression and prognostic value of VAVs in patients with AML were investigated using various databases, including GEPIA, CCLE, EMBL-EBI, UALCAN, cBioPortal, STRING, and DAVID. Blood samples from 35 patients with AML (non-M3 subtype) and 13 benigh individuals were collected at our center. VAV expression levels were detected by real-time quantitative PCR (RT-qPCR) and western blotting. Clinical data were derived from medical records. Results: Based on data from multiple databases, the expression levels of VAV1, VAV2, and VAV3 were significantly higher in AML than in control tissues ( P < 0.05). RT-qPCR and western blotting results showed that VAV expression in mRNA and protein levels were higher in patients with AML that in the control group ( P < 0.05). Complete remission rates were lower and risks were higher in patients with AML with high VAV1 expression than with low VAV1 expression ( P < 0.05). High levels of VAV2, VAV3, and VAV1 were related to a poor overall survival, and this relationship was significant for VAV1 ( P < 0.05). High expression levels of genes correlated with VAV1, such as SIPA1, SH2D3C, and HMHA1 were also related to a poor prognosis in AML. Functional and pathways enrichment analyses indicated that the contribution of the VAV family to AML may be mediated by the NF-κB, cAMP, and other pathways. Conclusion: VAVs were highly expressed in AML. In particular, VAV1 has prognostic value and is a promising therapeutic target for AML.

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