Expression Of Glucocorticoid Receptor In Patients With Chronic Lymphocytic Leukemia And Its Correlation With Prognosis

Objective: To study the expression of glucocorticoid receptor (GR) of mononuclearcells in peripheral blood of chronic lymphocytic leukemia (CLL) patients. To analyzethe correlation among the expression of GR subtypes including alpha, beta, gammaand P. To study on the relationship between GR expression and the prognosis of CLLpatients.Methods: Continuous samples of33chronic lymphocytic leukemia patients (10female and23male, median age62years old) hospitalized in our hospital from2009May to2013February were taken, as well as samples of32healthy controls (18females,14males, median age34years old).1Fasting elbow venous blood5ml in normal individuals and patients with CLLwas gathered. Peripheral blood mononuclear cells (PBMC) were collected usingFicoll density gradient centrifugation. Expression of GR α, GRβ, GRγ and GRpmRNA were detected by real-time fluorescence quantitative PCR and SYBR Green.2The correlation among the expression of GRα, GRβ, GRγ, GRP isoforms inCLL patients was analyzed by Spearman correlation.3Progression free survival (PFS) of the patients were analyzed. The medianfollow-up time was28(1~57) months. Kaplan-Meier survival curve was used toanalyze the effect of GR expression on patients PFS.Results: 1In the group of CLL patients, GR α mRNA expression amount was1210.25, theexpression of GRβ mRNA was39.42, the expression of GR γ mRNA was164.04,the expression of GRp mRNA was761.2The percentage of GR α, GR β, GR γ, GRP in patients group was55.65%,1.81%,7.54%, and35%respectively. While in the control group was64.82%,0.46%,18.73%, and15.9respectively.3The expression of GRαmRNA and GRP mRNA in patients group were higherthan that in control group,（P<0.05）. While the GRβ and GRγ mRNA expression inthe patient group and the control group showed no significant difference.4In CLL patients, GRp was positively correlated with GRαmRNA（P<0.05）. Butthere was no correlation between other receptor subtypes.5PFS in high GRαmRNA patients was significantly prolonged compared withthe lower GRαmRNA group, PFS in high GRp mRNA group were also significantlyprolonged compared with the lower GRp mRNA group.Conclusions:1The expression of GR alpha isoform in CLL patients occupies the absolutesuperiority, followed by subtype GRp, GRβ and GRγ, suggesting that GRαis themain effecting subtype.2The expression of GRαand GRp mRNA in patients with CLL were significantlyincreased compared with healthy controls, while the expression of GRβand GRγnosignificant difference between the patients and the control group. These datasuggested that GRα and GRp play a major role in the pathogenesis of CLL.3Patients with high GRαand high of GRp expression had a longer PFS,suggesting that GRα and GRp can be used in evaluating prognosis of CLL. HighGRαand GRp is a sign of good prognosis of CLL patients.4GRp was positively correlated with GRαmRNA in CLL patients, whileGRαmRNA were significantly increased, suggesting that GRp is likely to affect theprognosis of the patients by increasing the expression of GRα. Objective: To detect the serum macrophage migration inhibitory factor (MIF) level inchronic lymphocytic leukemia (CLL) patients, and analyze its relationship with otherprognostic factors of CLL. Investigate the effect of MIF on prognosis in CLL.Methods:1Continuous samples of33chronic lymphocytic leukemia patients (10femaleand23male, median age62years old) hospitalized in our hospital from2009May to2013February were taken, as well as samples of32healthy controls (18females,14males, median age34years old).2Serum MIF level were detected by ELISA in CLL patients and controls.3Analyze chromosome karyotypes of patients using R banding technique.4Mutations of P53in patients with CLL were detected by fluorescence in situhybridization (FISH) method.5Patients clinical indicators were detected, serum lactate dehydrogenase (LDH),peripheral blood lymphocyte count, serum β2micro protein level, etc.6Progression free survival (PFS) of the patients were analyzed, The medianfollow-up time was28(1~57) months. Kaplan-Meier survival curve was used toanalyze the effect of MIF on patients PFS.Results:1The serum MIF level in CLL patients (1199.79±691.01pg/ml) weresignificantly higher than the control group (176.74±105.82pg/ml)(P<0.01).Meanwhile, the serum MIF level had no significant difference between the patients inlate clinical stage (Binet B, C,1292.26±529.96pg/ml) and the patients in early stage(Binet A,1067.71±877.31pg/ml).2In the high LDH group (>250μ/L), the serum level of MIF patients was significantly higher than the low LDH group (<250μ/L), P<0.05; the serum level ofMIF patients in higher β2microglobulin group (>3mg/L) was significantly higherthan that of lower β2microglobulin group (<3mg/L), P<0.05. The MIF levels had nosignificant difference in the gender, age, white blood cell count, splenomegaly andabnormal karyotype of chromosome subgroups.3Detection of P53mutation by FISH in12CLL patients were negative.4According to the expression level of MIF,33patients with CLL were dividedinto high MIF group (a value higher than the medium) and low group (a value below),Analyzing prognosis of the two groups by Kaplan-Meier survival curves, resultsshow PFS had no significant difference in the two groups, P=0.875.Conclusion:1The serum MIF levels in CLL patients were significantly increased, MIF can beused as candidate markers for diagnosis of CLL, but should not be considered asindicators of disease progression.2In the high LDH group and high β2microglobulin group, the serum MIF levelswere significantly increased, suggesting that MIF were associated with the prognosisof CLL patients.3All patients had no detectable P53mutations, suggesting that MIF does notcause mutations in P53. The regulation of P53by MIF may occur in the translation ortranscription level.4MIF level has no effect on PFS of patients with CLL, so it is not considered asan independent prognostic factor. Objective: To detect the expression of miR-142-3P in chronic lymphocytic leukemia(CLL) patients, and its influence on prognosis; to explore the relationship betweenmiR-142-3p and glucocorticoid receptor isoforms in CLL patients.Methods:Continuous samples of33chronic lymphocytic leukemia patients (10femaleand23male, median age62years old) hospitalized in our hospital from2009May to2013February were taken, as well as samples of32healthy controls (18females,14males, median age34years old).1Fasting elbow venous blood5ml in normal individuals and patients with CLLwas gathered. Peripheral blood mononuclear cells (PBMC) were collected usingFicoll density gradient centrifugation. MiR-142-3p mRNA were detected by real-timefluorescence quantitative PCR and SYBR Green.2The correlation between miR-142-3p and GR isoforms was analyzed.3Based on experiment value of miR-142-3p mRNA, patients with CLL weredivided into high miR-142-3p expression group and low miR-142-3p expressiongroup, progression free survival (PFS) of each group was analyzes using Kaplan-Meier survival curves.Results:1The expression of miR-142-3p mRNA with a median value of0.86(0.559-2.75)in CLL patients was significantly higher than that in control group0.14(0.082-1.65),P <0.05.2The expression of miR-142-3p mRNA was negatively correlated with GR α and GRp in CLL patients, P <0.05. But there was no significant correlation betweenmiR-142-3p mRNA and GR β, GRγ.3PFS in high miR-142-3p expression group was shortened obviously comparedwith low miR-142-3p expression group. The PFS in two groups have significantdifference, P <0.05.Conclusion:1The expression of miRNA142-3p in CLL patients was significantly higher thanthat in control, suggesting that miRNA142-3p is closely related to the pathogenesis ofCLL.2The expression of miRNA142-3p in CLL patients were negatively correlated withGRα and GRp mRNA, suggesting that miRNA142-3p inhibits expression of GRα andGRp.3High level of miRNA142-3p expression is a negative prognostic factor, can beused as an independent indicator of prognosis of CLL patients.