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Objective: To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) . Methods: A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results: Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P =0.02, OR =0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P =0.02, OR =0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P =0.036, HR =0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P =0.024, HR =2.14, 95% CI 1.10-4.15) , leukemia transformation ( P <0.001, HR =2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P =0.012, HR =2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P =0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion: Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Ma, Yu, Ouyang, Luo, Pei, Xu, Hu, Mo, Xu, Lan, Shen, Shou, Qian, Feng, Zhao, Jiang, Hu, Zhang, Qian, Wu, Wu, Qiu, Li, Lang, Chen, Chen, Guo, Cao, Jiang, Xia, Le, Zhao, Huang, Zhang, Lv, Hua, Hong, Zheng, Wang, Hu, Chen, Zhang, Tao, Xie, Kuang, Luo, Su, Guo, Wu, Jiang, Zhang, Zhang, Chen, Xu, Guo, Tu, Hu, Yan, Yao, Lou, Jin and the APL Cooperative Group of Zhejiang Province.)

Bone loss is a prominent complication in immunologic thrombocytopenic purpura (ITP) patients with steroid treatment. Anti-osteoporotic medications are applied as a therapeutic strategy to prevent bone deterioration in ITP patients. However, the skeletal protective effect of alendronate (ALN) in ITP patients has been rarely reported. The present study was performed to determine whether ALN reduces bone loss in ITP patients. A total of 40 ITP patients with steroid treatment were randomized into a placebo group [n=20; caltrate D (CalD)] and an ALN (10 mg/day) + CalD group (n=20). The patients received CalD or CalD + ALN treatment for 9 months. The primary outcomes were bone mineral density (BMD) in the lumbar vertebrae (L1-L4), femoral neck and total hip, as well as bone metabolism markers. The results indicated that the BMD of the lumbar vertebrae (L1-L4), femoral neck and total hip was significantly increased after ALN + CalD treatment for at 6 and 9 months compared with the baseline. Compared with CalD treatment alone, CalD combined with ALN significantly elevated the BMD at the three skeletal sites at 9 months. Compared with the baseline levels or CalD treatment alone, ALN together with CalD treatment markedly reduced urinary Ca excretion and the serum levels of the bone resorption markers tartrate resistant acid phosphatase 5b and C-terminal telopeptides of type 1 collagen, at 9 months. In conclusion, treatment with ALN together with CalD significantly elevated the BMD at three skeletal sites, and inhibited urinary Ca excretion and the activity of bone resorption markers in patients with ITP.

Objective: We aim to explain the correlation among IL-18 gene polymorphism, its protein expression and LEDVT in the Chinese Han population., Methods: A total of 138 LEDVT patients and 150 healthy people volunteered as LEDVT and control groups. All the data, including the gender, age, BMI, levels of TG, LDL/HDL, TC, GLU, APTT, BUN, Cr, ALT, AST, ApoA1, ApoB, and Fg was detected. IL-18 level, IL-18 -137G/C and -607C/A polymorphism, and risk factors of LEDVT were detected using ELISA, PCR-RFLP and multivariate logistic regression analysis, respectively., Results: Increased BMI, GLU, Fg, BUN, ApoB and IL-18 and decreased APTT were found in the LEDVT group. The GC + CC genotype and C allele in -137G/C polymorphism was elevated in the control group when compared to that in the LEDVT group. The IL-18 level was elevated in the case group when compared to the control group with respect to the same genotype in -607C/A and -137G/C polymorphisms, and in the LEDVT group, IL-18 level was higher in the GG genotype than that in the GC + CC genotype of -137G/C polymorphism. BUN, GG genotype and IL-18 level were independent risk factors, but APTT was a protective factor of LEDVT., Conclusion: On the basis of our results, we concluded that the GG genotype of -137G/C polymorphism and IL-18 level are independent risk factors of LEDVT, and IL-18 gene polymorphism affects the level of IL-18 in LEDVT patients., (© 2017 Wiley Periodicals, Inc.)

Objective: Leukemia is characterized as a kind of malignant clonal disease in hematological stem cells. The study showed an abnormal level of DNA methylation in leukemia cells, which further led to an abnormal expression of hematological genes. This study investigated the role of miR-29b on the modulation of DNA methylation and tumor suppressor gene expression in leukemia patients., Patients and Methods: A total of 21 leukemia patients were recruited for the collection of monocytes. Methylation levels of promoter sequence of ESR1 and p15 genes were analyzed by methylation assay kit combined with DHPLC. DNA microarray and qRT-PCR were used to measure microRNA expressional profile, and bioinformatics plus luciferase reporter assay confirmed target gene of miR-29b. After transfection with miR-29b, promoter methylation levels of ESR1 and p15 gene were measured. Protein expressions of DNMT1 DNA (cytosine-5)-methyltransferase 1 (DNMT1), DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and DNA (cytosine-5)-methyltransferase 3B (DNMT3B) were quantified., Results: The methylation levels of the promoter region of ESR1 and p15 genes in monocytes of leukemia patient were significantly elevated (p < 0.05). DNA microarray and qRT-PCR confirmed the down-regulation of miR-29b (p < 0.05). Luciferase reporter assay revealed DNMT1, DNMT3A and DNMT3B as target genes of miR-29b. MiR-29b transfection inhibited the expressions of DNMT3A and DNMT3B in Kasumi-1 cells (p < 0.05), and promoter methylation levels of estrogen Receptor 1 (ESR1) and p15 gene were decreased (p < 0.05)., Conclusions: In leukemia cells, hyper- methylation existed in the promoter region of tumor suppressor gene. The methylation was enhanced in gene DNMT1, DNMT3A and DNMT3B via the reduction of miR-29b in leukemia tumor cells.

The objective of this article was to investigate the relationship between IRF-3 gene polymorphisms and the susceptibility and prognosis of CLL. Between January 2011 and August 2012, 108 CLL patients and 112 healthy were enrolled in the study. DHPLC and Shesis software were applied in our study. In rs7251, CG genotype may increase the CLL risk. In the rs2304206, the alleles T may increase the CLL risk. The GTC haplotype can decrease the CLL risk in normal people, the GTT haplotype can increase the CLL risk in normal people. After treatment, in the rs7251, the event-free survival (EFS) in patients carrying CC genotype was higher than those carrying CG + GG genotype. In the rs2304206, the EFS in patients carrying CC genotype was higher than those carrying CT + TT genotype. IRF-3 gene polymorphisms were associated with the susceptibility and prognosis of CLL, it can be used as an auxiliary index for clinical detection of CLL.

Objectives: This meta-analysis investigates the prognostic effect of SET binding protein 1 (SETBP1) mutations in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL)., Methods: Eligible studies from Pubmed, Embase, and Web of Science were searched from database inception through April 2016. Hazard ratios (HRs) and 95% confidence interval (CI) of overall survival (OS) were pooled to calculate the prognostic significance of SETBP1 mutation in patients., Results: A total of 12 studies with 2321 patients were included in this meta-analysis; 4 studies for MDS, 5 studies for CMML, and 3 studies for CNL. Pooled results suggested that MDS and CMML patients with SETBP1 mutations had a significantly poorer prognosis when compared with patients with wild-type SETBP1 (MDS: HR = 1.808, 95% CI (1.218-2.685), P = 0.001; CMML: HR = 2.223, 95% CI (1.493-3.308), P<0.001). SETBP1 mutations in CNL patients however, showed no significant effect on the overall survival (HR = 1.773, 95% CI (0.877-3.582), P = 0.111). The Begg's and Egger's tests did not show significant publication bias in any groups., Conclusions: Current evidence shows that SETBP1 mutation is associated with a poor prognosis in patients with MDS and CMML, but not in patients with CNL., Competing Interests: The authors have declared that no competing interests exist.

Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. Methods uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. Results uPAR level in bone marrow fluid of MM patients (1.52±0.32 μg/ml) was found to be higher than that in the control group (0.98±0.15 μg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. Conclusion Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

Objective: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis., Methods: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules., Results: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes., Conclusions: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.