ABSTRACT
Objective To investigate the effects RORrt (RORrt),IRF8 (IRF8) and STAT3 (STAT3) in peripheral blood CD4+T cells on the cell proliferation and differentiation in elderly patients with iron-overload myelodysplastic syndrome(MDS).Methods A prospective case-control study was conducted.Twenty-two elderly hospitalized patients(12 males and 10 females)aged 60-78 years with iron-overload MDS from Jan.2017 to Dec.2018 were enrolled and considered as the observation group.Twenty MDS patients without iron overload hospitalized in the same period were selected as the non-iron overload group,and 26 healthy elderly people were considered as the healthy control group.Peripheral blood monocytes(PBM)were prepared and resident CD4+T cells were sorted by flow cytometry.The mRNA and protein expression levels of transcription factors of RORrt,p-STAT3 and IRF8 were detected by quantitative real time polymerase chain reaction(qRT-PCR)and Western blotting.Results In peripheral blood CD4+T cells,the mRNA expression level of RORrt and p-STAT3 were higher and that of IRF8 was lower in the iron-overload group than in the non-iron overload group and the healthy control group(42.634± 18.613 vs.21.289 ± 15.158 and 22.520 ± 9.896;29.710±9.689 vs.12.355±4.681 and 9.818±3.845;19.293±8.258 vs.23.785±12.498 and 69.619±23.768,P＜0.01).In peripheral blood CD4+T cells,the protein expression level of RORrt and p-STAT3 was higher,and that of IRF8 was lower in the iron overload group than in the non-iron overload group and healthy control group(P＜0.01).Conclusions The abnormalities of the mRNA and protein expression levels of transcription factors of RORrt,IRF8 and p-STAT3 in CD4+ T cells play a fundamental role in the pathogenesis of iron overload MDS in elderly patients.
ABSTRACT
Objective To study the significance of Th17 cells in patients with myelodysplastic syndrome (MDS) and iron overload.Methods A total of 77 patients with MDS admitted to Guangzhou First People's Hospital were enrolled from January 2017 to December 2018,who were divided into iron overload group (37 cases) with serum ferritin (SF) over 1000 μg/L and non-ferrous overload group(40 cases).CD4+T cells in peripheral blood (PB) and bone marrow (BM) were sorted by flow cytometry.The ratio of Th17 cells and cells with abnormal karyotype were compared.IL-17 and IL-6 protein and RNA expression were detected by ELISA and quantitative real-time PCR(qRT-PCR).Results The proportions of Th17 cells in PB and BM in iron overload group were significantly higher than those in non-iron overload group [(41.06± 0.96)％ vs.(26.80± 1.21)％;(47.39± 1.60)％ vs.(34.29± 1.03)％;P＜0.01].The Th17 positive cells with abnormal karyotype in iron overload group were more than those in non-iron overload group[(4.96±0.53)％ vs.(3.67±0.12)％ in PB;(10.06±1.67)％ vs.(4.36±0.43)％ in BM;P＜0.01].Similarly,the protein levels as well as mRNA expression of IL-6 and IL-17 in patients with iron overload were significantly higher than those in non-iron overload group (P＜0.01 both in PB and BM).Conclusions As hematopoietic regulators secreted by Th17 cells,the expression of IL-6 and IL-17 in MDS patients with iron overload are elevated.This may predict the influence of these factors to the differentiation of Th 17 cells.
ABSTRACT
Objective To evaluate the efficacy of CHOP (cyclophosphamide,doxorubicin,vincristine,and prednisone)chemotherapy on peripheral T cell lymphomas-unspecified (PTCL-U)in patients aged 80 years and over,and investigate the chemotherapy adverse effects and its prognostic factors.Methods Clinical data of 57 patients with PTCL-U confirmed by pathology and immunohistochemistry in Guangzhou First People's Hospital from January 2008 to January 2015 were retrospectively analyzed.The efficacy and adverse effects of CHOP chemotherapy,and its prognostic factors were evaluated.Results Of 57 patients,11 (19.3％) achieved complete remission,23(40.4％)had partial remission,14(24.6％)had stable disease,and 9(15.8％)had progressive disease after CHOP chemotherapy,with a total effective rate of 59.6％ (34 cases).The expected 1-year,2-year and 3-year overall survival(OS)rate was 70.2％ (40 cases),36.8％ (21 cases) and 17.5％ (10 cases),respectively.The median survival time was 18.2 months.Among the 57 patients,40(70.2％) had hypoplasia of bone marrow at degree Ⅰ-Ⅱ,17 (29.8％) at degree Ⅲ-Ⅳ,49 (86.0％) had mild nausea and vomiting(degree Ⅰ-Ⅱ),8(14.0％)had severe nausea and vomiting(degree Ⅲ-Ⅳ),7 had liver dysfunction,2 had cardiac toxicity and 7 had disturbance of blood coagulation.Univariate analysis showed that the alkaline phosphatase,Ki-67 percentage,lymphoma international prognostic index(IPI)score,extranodal involved sites(＞1),as well as the efficacy and course of chemotherapy were the prognostic factors for survival time in very elderly patients.Multivariate analysis indicated that IPI score＞2(95％CI:1.12～6.35,x2 ＝5.45,P＜0.01),extranodal involved sites(＞1)(95％ CI:2.58-15.32,x2 ＝ 16.42,P＜0.01),disease progression(95％CI:1.82～12.15,x2 ＝ 10.23,P＜0.01),chemotherapy courses(＞4) (5％CI:0.18～0.79,x2 ＝7.28,P＜0.01)were the independent prognostic factors for the median survival time in very elderly patients.Conclusions PTCL U patients aged 80 years and over have poor prognosis.CHOP chemotherapy has a certain effect on PTCL-U in very elderly patients,and chemotherapy side effects can be tolerated.IPI score＞2 and extranodal involved sites(＞ 1)are the important prognostic factors in very elderly PTCL-U patients.The completion of full course of chemotherapy with remission occurrence is important to prolong survival time in very elderly PTCL-U patients.
ABSTRACT
Objective To detect the expressions of c-myc,Bmi-1,serum insulin-like growth factor-Ⅰ (IGF-Ⅰ) and insulin-like growth factor binding protein-3 (IGFBP-3) in diffuse large B-cell lymphoma (DLBCL),and to analyze their relations with clinical stages,efficacy and prognosis.Methods 102 cases of incipient patients with DLBCL and 60 patients or health examination volunteers were chosen as DLBCL group and control group,respectively.Immunohistochemical method was used to detect expressions of c-myc and Bmi-1 in DLBCL wax samples.Chemiluminescence immunoassay method was used to determine the levels of serum IGF-Ⅰ and serum IGFBP-3.The expression differences of these factors between DLBCL group and control group and their relations with pathological types,clinical stage,IPI and chemotherapy were analyzed.Results The positive rates of c-myc and Bmi-1 were 71.6 ％ (73/102) and 61.8 ％(64/102) in the tissues of DLBCL,respectively.The positive rates of c-myc and Bmi-1 in non-GCB group were higher than those in GCB group [c-myc:80.0 ％ (48/60) vs 59.5 ％ (25/42);Bmi-1:71.7 ％ (43/60) vs 50.0 ％ (21/42)].With the increase of IPI score,the expressions of c-myc and Bmi-1 were enhanced,but there were no statistical differences between Ⅲ-Ⅳ group and Ⅰ-Ⅱ group (P ＞ 0.01).The differences of 3-year progression free survival (PFS) rate and 3-year overall survival (OS) rate between c-myc gene or Bmi-1 gene normal and abnormal had statistical significance,and 3-year PFS rate and 3-year OS rate of double-hit of c-myc gene and Bmi-1 were lower.C-myc gene and Bmi-1 gene aberrant were the independent prognosis factors.The levels of serum IGF-Ⅰ and serum IGFBP-3 in DLBCL group were significantly lower than those in the control group (P ＜ 0.01),however,the levels were increased after chemotherapy (P ＜ 0.01).Serum IGF-Ⅰ and serum IGFBP-3 levels had no significant differences between non-GCB group and GCB group (P ＞ 0.01).Their levels in stage Ⅳ group or high risk group were significantly lower than those in other groups.Serum IGF-Ⅰ level and serum IGFBP-3 level had no significant differences between the c-myc gene or Bmi-1 gene abnormal group and normal group (P ＞ 0.01),but their levels were lower in both c-myc gene and Bmi-1 gene abnormal group than those in normal group.Conclusions C-myc and Bmi-1 are related with the biological characteristics and prognosis of DLBCL.Serum IGF-Ⅰ level and serum IGFBP-3 level reflect clinical stages of DLBCL and the efficacy in a certain degree.The expressions of c-myc and Bmi-1 have some correlation with the levels of serum IGF-Ⅰ and IGFBP-3 in DLBCL.