IL-10 as an Indicator for Predicting Clinical Progression in Acute Lymphoblastic Leukemia Patients.

BACKGROUND: The aim of this research was to estimate the expression of interleukin-10 in acute lymphoblastic leukemia (ALL) patients before and after chemotherapy in order to evaluate its role as a marker of disease progression. METHODS: Flow cytometry was used to detect the serum IL-10 levels in ALL patients before and during chemotherapy. Patients were divided into either complete remission (CR) group and non-remission (NR) group, before chemotherapy group and during chemotherapy group, B-ALL group and T-ALL group, WT-1 positive group and BCR-ABL1 positive group. The changes in serum IL-10 concentration before and during the chemotherapy were analyzed. RESULTS: IL-10 serum levels were significantly elevated in ALL patients at the onset of disease, and it was also more elevated in the NR group compared to the CR group. There is a significant reduction in IL-10 serum levels in ALL patients after effective chemotherapy. There was no significant difference between the before chemotherapy group and during chemotherapy group. Regardless of chemotherapy, the IL-10 levels of patients whose bone marrow achieved complete remission were lower than the patients who have not (p < 0.05). The same result can be seen in B or T-ALL groups. There was no significant difference in IL-10 serum levels between the group with WT-1(+) or BCR-ABL1(+) and the group with WT-1(-) or BCR-ABL1(-) (p > 0.05). In some ALL patients, increased IL-10 concentrations may be correlated to the number of peripheral blood leukemic cells. CONCLUSIONS: The increase of serum IL-10 level may be a possible marker of disease progression in ALL.

Identification of dyslipidemia as a risk factor for sudden sensorineural hearing loss: A multicenter case-control study.

BACKGROUND: Recently, several studies have reported an association between lipid profiles and sudden sensorineural hearing loss (SSNHL), yet there is considerable variability between the individual studies in defining the precise association between serum lipids levels and SSNHL. This study sought to identify a possible relationship between dyslipidemia and the prevalence and prognosis of SSNHL. METHODS: A case-control study was carried out at two independent medical centers, including 2,288 SSNHL patients and 2,288 healthy controls. Clinical characteristics and serum lipid parameters were assessed, including total cholesterol (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (Trig), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), and lipoprotein a (Lpa). Multivariate logistic regression analysis was performed to assess the relationship between lipid profiles and SSNHL in the 4,576 subjects. RESULTS: Significant differences were identified in several conventional serum lipid markers including CHOL, Trig, HDL, LDL, ApoAI, ApoB, and Lpa, between SSNHL patients and healthy controls. Serum ApoAI levels were significantly lower in patients with bilateral SSNHL compared to unilateral SSNHL. Binary logistic regression analysis revealed that higher levels of ApoB, LDL, Trig, and lower levels of ApoAI and HDL were all associated with an increased risk of SSNHL. After clinical characterization, multivariate analysis showed that only low levels of ApoB predicted likelihood of a recovery of more than 30 dB among patients with SSNHL. CONCLUSIONS: Serum lipids are associated with the incidence and prognosis of SSNHL. Identification of dyslipidemia may improve early evaluation and management of SSNHL risks.

Genome-Wide Methylation Patterns in Androgen-Independent Prostate Cancer Cells: A Comprehensive Analysis Combining MeDIP-Bisulfite, RNA, and microRNA Sequencing Data.

This study aimed to investigate the mechanisms underlying the development of the androgen-independent phenotype in prostate cancer. Methylation patterns were detected in androgen-independent and androgen-dependent lymph node carcinoma of the prostate (LNCaP) prostate carcinoma cells based on methylated DNA immunoprecipitation-bisulfite sequencing data and differentially methylated regions (DMRs) were identified. Differentially expressed genes (DEGs) and micro RNAs (miRNAs) with DMRs (named MDEGs and MDEmiRNAs) were identified by combining transcriptome and methylation data, and transcription factor (TF)-DEGs with DMRs in promoter (PMDEGs) and MDEmiRNA-MDEGs networks were constructed. Furthermore, a time-course analysis of gene transcription during androgen deprivation was performed based on microarray data and DMRs, MDEGs, and DEmiRNAs were validated. In total, 18,447 DMRs, 3369 MDEGs, 850 PMDEGs, and 1 MDEmiRNA (miR-429) were identified. A TF-target network (94 PMDEGs and 5 TFs) and a miRNA-target network (172 MDEGs and miR-429) were constructed. Based on the time-course analysis of genes in the networks, NEDD4L and PBX3 were targeted by SOX5, while GNAQ, ANLN, and KIF11 were targeted by miR-429. The expression levels of these genes and miR-429 were confirmed by quantitative real-time polymerase chain reaction. Additionally, 109 DMRs were confirmed using additional public datasets. The regulatory pathways SOX5-NEDD4L/PBX3, miR429-GNAQ/ANLN-RHOA, and miR429-ANLN-KIF11 may participate in the progression of the androgen-independent phenotype in prostate cancer.

Expression of CD56 is a risk factor for acute lymphocytic leukemia with central nervous system involvement in adults.

OBJECTIVE: To gain further insights into the predisposing risk factors for central nervous system (CNS) involvement in patients with acute lymphocytic leukemia (ALL), the impact of CD56 expression in these patients was investigated. METHODS: We reviewed the clinical features of CD56 expression in 588 consecutive ALL patients treated with systemic chemotherapy regimens between 2000 and 2014. The categorical data from CD56+ ALL patients were compared with those from CD56- ALL patients. RESULTS: Among the 588 patients studied, 18.9% showed CD56 expression. The expression was significantly associated with CD33+, CD10-, CD15+, TdT-, and CD5+ immunophenotypes. After systemic chemotherapy, 8.8% patients showed CNS involvement, of which 3.2% exhibited combined recurrences and 5.6% exhibited isolated CNS involvement. The 5-year event-free survival was significantly lower for patients with CD56+ immunophenotype compared with patients with CD56- immunophenotype (22.5% vs. 32.7%, P = 0.04). Cumulative incidences of CNS involvement were significantly greater in the CD56+ cohort compared with the CD56- cohort (14.4% vs. 7.5%, P = 0.02). Multivariate analysis revealed CD56 expression to be statistically significant risk factors for CNS involvement. CONCLUSION: CD56 expression should be regarded as an independent risk factor for ALL with CNS involvement in adults.

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia.

Despite the outstanding advances made over the past decade regarding our knowledge of acute leukemia (AL), relapsed AL remains to be associated with a dismal prognosis. A better understanding of AL relapse and monitoring of the D-dimer and lactate dehydrogenase (LDH) plasma levels following chemotherapy may aid clinicians in determining whether relapse may occur in the subsequent phases of the disease. The present study evaluated D-dimer and LDH levels in 204 patients with relapsed AL. Data were collected at the initial onset of AL, at complete remission (CR) and in patients with relapsed AL. D-dimer plasma levels were significantly increased in patients with initial AL and in patients with relapsed AL (P=0.005 and P=0.007, respectively) but not in those with CR. LDH levels were significantly increased in AL patients at the initial onset of disease and at relapse compared with patients achieving CR, irrespective of cell type. Plasma prothrombin time, activated partial thromboplastin time and fibrinogen levels were not significantly different across patients (with the exception of acute promyelocytic leukemia patients) at the initial onset, relapsed AL or CR. Routine hematological parameters (white blood cell count, hemoglobin, platelet count) were significantly different at the initial onset of AL (P=0.002, P<0.001 and P=0.001, respectively) and during relapsed AL (P=0.009, P=0.003 and P<0.001, respectively) compared with patients achieving CR, suggesting an association between D-dimer, LDH and relapsed AL. These results also indicate that determination of D-dimer and LDH levels may be useful for predicting the probability of relapse during chemotherapy, but should also be combined with routine hematological parameters.

A novel mutation of SETBP1 in atypical chronic myeloid leukemia transformed from acute myelomonocytic leukemia.

To investigate an oncogenic mutation of SETBP1 in the evolution from acute myelomonocytic leukemia (M4) to secondary aCML. Clinical data and molecular studies were analyzed of paired aCML and 'normal'DNA from a case with M4. We identified a mutation in SETBP1 (encoding a p.Asp868Ala alteration). The analysis of paired sample indicated that SETBP1 mutation was acquired during leukemic evolution.

Decreased programmed death-1 expression on the T cells of patients with ankylosing spondylitis.

BACKGROUND: Programmed death-1 (PD-1) plays a vital role in down-modulating immune responses and maintaining peripheral tolerance. METHODS: The authors have investigated the inducible expression of PD-1 on activated T cells from patients with ankylosing spondylitis (AS). Thirty patients with AS and 31 unrelated healthy controls (HCs) were recruited in this study. The expression of PD-1 on T cells harvested from nonstimulated (t0) or stimulated cultures with phytohemagglutinin for 24 hours (t24) was determined by flow cytometry. The multiple levels of the PD-1 expression on stimulated and nonstimulated cells from each individual's sample (t24/t0) represented as the degree of the inducible effect on PD-1 expression. RESULTS: The expression of PD-1 on nonstimulated T cells presented no significant difference between AS group and HC group (P > 0.05). After stimulation, the degree of effect on PD-1 expression of CD4+, CD4+CD25+, CD4+CD25 high, CD4+CD25 low and CD4+CD25- T cells were significantly lower in patients with AS than those in HC group (1.9 ± 0.9 versus 3.6 ± 2.3, 9.7 ± 7.4 versus 17.8 ± 12.6, 87.8 ± 48.6 versus 157.3 ± 117.0, 3.7 ± 1.4 versus 7.3 ± 2.4, 0.5 ± 0.3 versus 1.1 ± 0.6, respectively, P < 0.05). However, there was no significant difference of the effect on all lymphocytes and CD8+ T cells between patients with AS and HCs (P > 0.05). CONCLUSIONS: The decreased inducible expression of PD-1 on active T lymphocytes, especially on CD4+CD25 high and CD4+CD25+ T cells, may be one of important factors involved in the development of AS.

Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males.

INTRODUCTION: Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa. MATERIAL AND METHODS: 120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression. RESULTS: 5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues. CONCLUSIONS: The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa.

Association of short tandem repeat polymorphism in the promoter of prostate cancer antigen 3 gene with the risk of prostate cancer.

BACKGROUND: PCA3 (prostate cancer antigen 3) gene is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 mRNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In our study, we evaluated whether there is polymorphism in PCA3 promoter region and also assess the association of the polymorphism with prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: We designed a specific primer set to screen the promoter of PCA3 gene by polymerase chain reaction (PCR)-based cloning and sequencing with the DNA extracted from peripheral blood samples of prostate cancer (PCa) cases (n = 186) and healthy control cases (n = 135). Genotype-specific risks were estimated as odds ratios (ORs) with associated 95% confidence intervals (CIs) by chi-square test. Possible deviation of the genotype frequencies from controls and PCa cases expected under Hardy-Weinberg equilibrium was assessed by the chi-square test. Short tandem repeat polymorphism of TAAA was found in the promoter region of PCA3 gene, five polymorphisms and eight genotypes were identified. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. The group 11TAAA and ≥12TAAA were associated with higher relative risk for prostate cancer than group ≤10TAAA (OR = 1.76, 95%CI = 1.07-2.89[for group 11TAAA]; OR = 5.28, 95%CI = 1.76-15.89[for group ≥12TAAA]). CONCLUSIONS/SIGNIFICANCE: The presence of the (TAAA)n short tandem repeat polymorphisms in the PCA3 promoter region may be a risk factor for prostate cancer in the Chinese population.