[The Role and Mechanism of MiR-451 in Multidrug Resistance of Leukemia Cell Line K562/A02].

OBJECTIVE: To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia. METHODS: CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups. RESULTS: The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01). CONCLUSION: There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.

Expression of CD123 Related Long Non-coding RNA in Acute Myeloid Leukemia Bone Marrow Mononuclear Cells and Its Clinical Significance.

Acute myelogenous leukemia (AML) is a very common hematopoietic malignancy. Hematopoietic stem cell transplantation can improve the therapeutic effect of AML, but the 5-year survival rate is very low. CD123 imbalance, abnormal gene expression, and epigenetics play an important role in the pathogenesis of AML. This research was to explore the differential expression of CD123-related long non-coding RNA (lncRNA) in AML bone marrow mononuclear cells and provide a theoretical basis for targeted therapy of AML. High-throughput sequencing was performed to screen differentially expressed lncRNA in bone marrow mononuclear immunophenotypes of CD123+ and CD123- from patients with primary AML, and real-time quantitative PCR was adopted for screening and validation. There were 933 differentially expressed lncRNAs in the CD123+ group and the CD123- group, 407 lncRNAs were up-regulated and 463 lncRNAs were down-regulated in the CD123+ group. 14 lncRNAs with more than 2 times of difference were screened for identification, and it was found that compared with CD123- group, there was no substantial difference in the expression of JHDM1D-AS1, LINC01355, CASC15, FAM13A-AS1, HSPC324, LOC339803, LINC00877, and MAG12-AS3 in CD123+ group (P>0.05). The expressions of LOC101929698, BaALC-AS2, BOLA3-AS1, and FBX19-AS1 were considerably up-regulated (P<0.05), while the expressions of LOC100132249 and LINC02085 were considerably down-regulated (P<0.05). In summary, differentially expressed lncRNAs in bone marrow samples of CD123+ and CD123- group of newly diagnosed AML patients may be involved in the process of AML and seriously affect the prognosis of patients.

Rituximab combined with GDP regimen can effectively improve the efficacy and immune function of non-Hodgkin lymphoma.

OBJECTIVE: To evaluate the efficacy of rituximab combined with GDP regimen (gemcitabine + cisplatin + dexamethasone) in the treatment of non-Hodgkin lymphoma and its impact on the immune function of patients. METHODS: Clinical data of 88 patients with non-Hodgkin lymphoma (NHL) treated in Affiliated Hospital of Yan'an University from February 2017 to February 2019 were analyzed retrospectively. Among them, 40 patients treated with the second-line regimen (gemcitabine + cisplatin + dexamethasone) were served as the control group, and 48 patients received additional rituximab were as the observation group. The therapeutic effect, incidence of adverse reactions, levels of complement (C3, C4) and immunoglobulin [immunoglobulin (Ig) G, IgM, IgA] before and after treatment were compared between the two groups. Cox regression analysis was used to analyze the prognostic factors of patients. RESULTS: The total response rate of patients in observation group was higher than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions (hair loss, nausea and vomiting, thrombocytopenia, anemia and bone marrow suppression) between the two groups (P>0.05). After treatment, the levels of C3 and C4 in both groups were lower than those before treatment, and the decrease in observation group were more evident than that in control group (P<0.05). No notable fluctuation was observed in the levels of IgG, IgM and IgA in both groups between before and after treatment (P>0.05). Cox regression analysis found that Ann Arbor stage and pretreatment disease status were the factors affecting the prognosis of patients. CONCLUSION: Rituximab combined with GDP regimen has a significant effect on the treatment of non-Hodgkin lymphoma, and Ann Arbor stage and pretreatment disease state are prognostic factors for patients with NHL.

Immuno-phenotypes and prognosis of acute leukemia in elderly patients.

OBJECTIVE: This study is to provide reliable experimental treatment options for the diagnosis of acute leukemia, prognosis analysis and the detection of minimal residual disease. We observed the bone marrow CD123/CD117/CD34/HLA-DR antigen expression in 64 elderly patients with acute leukemia (AL). METHODS: The immune phenotypes of 64 elderly AL patients were detected and the correlations of CD123, HLA-DR, CD34 and CD117 expression with the leukemia cell morphology were analyzed. The cell genetics, molecular biology and the prognostic stratification were compared based on flow cytometry. RESULTS: In CDl23-positive patients, the complete remission (CR) rate was 21.5%. In CDl23-negative patients, the CR rate was 59.1%. The CR rate was 21.9% in HLA-DR-positive patients and 43.8% in HLA-DR-negative patients. The CR rate was 24.0% in CD34-positive patients and 41.1% in CD34-negative patients. The CR rate was 29.0% in CD117-positive patients and 42.3% in CD117-negative patients. The CR rate was 34.4% in CD38-positive patients and 0.00% in CD38-negative patients. CONCLUSIONS: These results suggest that CD123(+), CD117(+), CD34(+), and HLA-DR(+) are the factors related with the poor prognosis of elderly patients with acute leukemia.