Adult ; Cladribine/therapeutic use* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans

OBJECTIVETo explore the correlation between JAK/STAT signaling pathways and pathogenesis of immune thrombocytopenia(ITP).

METHODSTwenty-six newly-diagnosed ITP patients was included in this study. They all meet the clinical and hematological criteria for the diagnosis of ITP, and patients with coronary heart disease, severe refractory hypertension, diabetes or with severe liver or kidney function incompetence were ruled out. 24 healthy control without autoimmune diseases, viral infectious diseases and with normal liver and kidney functions were also included. The expressions of Jak3, p-Jak3 mRNA, Stat3, and p-Stat3 were tested and the changes in levels of IL-21 mRNA, IL-21 cell secretion after DEX intervention and AG490 blockade were measured.

RESULTSCompared with the healthy control, patients with ITP had significantly high expressions of Jak3, p-Jak3 mRNA, Stat3 and p-Stat3 protein, which significantly reduced after AG490 blocking (P<0.01). The expression of IL-21 mRNA and the secretion of IL-21 obviously decreased after DEX intervention, but increased after AG490 blocking(P<0.01).

CONCLUSIONThe pathogenesis of ITP associates with the activation of JAK/STAT signaling pathways, and IL-21-mediated JAK/STAT signaling pathways play regulatory role in ITP.

Humans ; Interleukins ; Purpura, Thrombocytopenic, Idiopathic ; STAT3 Transcription Factor ; Signal Transduction

OBJECTIVE: To explore the characteristics of cytogenetics and molecular genetics in patients with multiple myeloma(MM). METHODS: Fluorescence in situ hybridization(FISH) was used for molecular genetics analysis in 86 cases of newly diagnosed MM, at the same time the chromosome karyotype analysis was performed in 20 cases. Specimen were bone marrow cells. RESULTS: FISH detection showed that 68 cases of MM (79.07%) had at least one type of the molecular genetic abnormalities. The positive rates of IgH rearrangement, 1q21 amplification, D13S319 deletion, RB1 deletion and.P53 deletion were 62.79%, 26.74%, 24.42% ,13.95% and 1.16%, respectively. The positive rate of IgH was significantly higher than that of any other probes(P<0.01). The positive rate of IgH was 79.41% in 68 cases. Out of which the positive rate of IgH single and combined with 1, 2, 3, 4 probes was 59.26%, 24.07%, 11.11%, 5.56% and 0 respectively. The positive rate of IgH only was very signficantly higher than that of combined with any other probes(P<0.01).The positive rate of 1q21 was 33.82% in 68 cases, Out of which the positive rates of 1q21 or combined with 1,2,3,4 probes was 21.74%, 43.48%, 21.74%,13.04% and 0 respectively, the 1q21 probe showed positive as combined with other probes(P<0.01), especially with IgH(P<0.05). The positive rates of D13S319 were 30.88% in 68 cases of patients, out of which the positive rates of D13S319 single or combined with 1, 2, 3, 4 probes was 14.29%, 28.57%, 42.86%, 14.29% and 0 respectively, the D13S319 combined with other probes appeared more significant positive(P<0.01), especially with 1 or 2 probes (P< 0.01). The positive rate of RB1 was 17.65% in 68 cases, the positive rate of RB1 singl or combined with 1, 2, 3, 4 probes were 0, 25%, 50%, 25% and 0, the RB1 appeared positive always combined with other probes, especially with D13S319 probe (P<0.01). The positive rate of P53 was 1.47%, as combined with RB1 and D13S319 probes. The chromosomal karyotyping showed that 3 cases carried abnormal chromosomal and 17 cases carried normal chromosome, Out of which 17 cases showed positive by FISH. There was a significant difference of sensitivity between FISH combined with chromosome karvotyping and single chromosome karvotype (P< 0.01). CONCLUSION The genetic abnormalies display obvious heterogenicity in MM. The sensitivity of FISH is higher than that of chromosomal karvotyping. If FISH and chromosome karvotyping are combined, the positive rate of abnormality can be raised.
Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; genetics ; Retrospective Studies

OBJECTIVE: To evaluate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) on patients with multiple myeloma( MM) after Sequential different chemotherapy. METHODS: Seven cases of patients with MM were included in the A group, and 14 cases of patients received 4-6 courses of chemotherapy with VAD and MP before transplantation were included in the B group and received 4-6 courses of chemotherapy with VTD and VD before transplantation. Auto-peripheral blood hematopoietic stem cell were mobilized by G-CSF. Condition regimen were melphalan(A group) or bortezomib combined melphalan(B group). IFN-α(A group) or Thalidomide(B group) was used as maintenance treatment after auto-PBHSCT. RESULTS: Two cases of patients reached to complete remission (CR)(2/7,28.6%),1 case got very good partial remission (VGPR) (1/7,14.3%), 4 cases got partial remission(PR) (4/7,57.1%) in A group, and 9 cases got CR (9/14,64.3%), 3 cases got VGPR(3/14,21.4%), and 2 cases got PR(2/14,14.3%) in the B group before auto-PBHSCT. The CR and VGPR were significant difference between 2 groups (P<0.05). All the patients got hematopoietic recovery. In 2 groups, the median time of ANC recovery≥0.5×10/L was 13 (11-16) and 14（11-18）days, that of WBC recovery ≥4.0×10/L were 16(15-19) and 18(16-20)days, Plt recovery ≥ 50 ×10/L was 21 (18-25) and 21(17-25) days. Bone marrow showed CR in 21 to 28 days after transplantation. All of 7 cases of patients remised in 6 to 47 months after transplantation, and 4 cases died lastly and 3 cases failed to be followed up in A group. The median time of progression-free survival(PFS) was 36(6-47) months, and that of overall survival(OS) was 37(7-50) months. In B group, 2 cases of patients remissed in 5 and 17 months after transplantation, and did lastly, 1 case relieved in 12 months after transplantation and failed to be followed up. 1 case of patient relived in 46 months after transplantation, and then received the second auto-PBHSCT, and got CR for 105 months. Other 10 cases got CR, their median time of PFS was 45.5(4-105) months, the median time of overall survival(OS) was 45.5(4-105) months. The PFS and OS were very significant different between 2 groups (P<0.01). CONCLUSION Bortezomib-based chemotherapy, Auto-PBHSCT and maintenance treatment with thalidomide were favorable to the patients of MM for survival prolongation.
Antineoplastic Combined Chemotherapy Protocols ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Myeloma ; therapy ; Peripheral Blood Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo investigate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT) combined with adoptive immunotherapy for patients with B lymphocyte malignant lymphoma(ML).

METHODSA total of 110 cases of ML treated with adoptive immunotherapy after auto-PBHSCT from January 2000 to December 2009 were enrolled in adoptive immunotherapy group (treated group), while 74 cases of ML treated without adoptive immunotherapy after auto-PBHSCT from January 1995 to December 1999 were used as control group. The efficacy of 2 groups were analyzed and compared, 110 case of ML in treated group included 78 cases of non-Hodgkin's lymphoma(NHL), 32 cases of Hodgkin's lymphoma(HL),74 cases of ML in control group included 52 NHL and 22 HL. All of the patients were treated sequentially with chemotherapy regimens for 6 courses. After that, all the patients received auto-PBHSCT. After hematopoietic reconstruction, the patients in treated group were given 6 courses of adoptive immunotherapy(rhIL-2 100 WU/day for 10 days monthly for each course), while the patients in control group were not given immunotherapy. All the patients were followed-up for more than 5 years.

RESULTSThere was one patient in each group, who died of liver failure and cerebral hemorrhage respectively within 3 and 2 months, and all the other patients achieved hematopoietic reconstruction. Following-up for 1, 3, 5 years, the disease-free survival (DFS) rate in treated group was 97.3%,93.6%,87.3% while 91.9%, 73.0%, 64.9% in control group. Following-up for 3 and 5 years, there was very significant difference in DFS between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of patients in stage I/II and III/IV in the treated group were 100%,100%,91.7% and 96.5%,91.9%,86.0% respectively while DFS of control group was 100%, 93.3%, 86.7% and 89.8%, 67.8%, 59.3%, there was a significant difference in 3 and 5 years DFS of III/IV stage patients between 2 groups (P<0.01). The 1,3 and 5 year DFS rate of HL patients were 100%, 93.8%,84.4% in treated group and 100%,72.7%,59.1% in control group respectively. There was significant difference in 3 and 5 years DFS of HL between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of stage I/II HL patients were 100%,100%,88.9% in treated group and 100%,100%,80.0% in control group. The 1,3 and 5 year DFS of HL patients in stage III/IV was 100%,91.3%,82.6% and 94.1%,64.7%,52.9% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage of HL patients between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of NHL patients is 96.2%, 93.6%,88.5% in treated group and 90.4%,73.1%,65.4% in control group respectively. There was a significant difference in 3 and 5 years DFS of NHL between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of stage I/II NHL patients was 100%, 100%, 93.3.9% in treated group and 100%, 90%, 90.0% in control group, respectively. The 1,3 and 5 year DFS of NHL patients in stage III/IV is 95.2%, 92.1%,87.3% and 88.1%,69.0%, 59.5% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage NHL patients between 2 groups (P<0.05).

CONCLUSIONTherapeutic efficacy is satisfactory for the patients of B lymphocyte ML treated with adoptive immunotherapy after auto-PBHSCT, especially benefited the patients of stage III/IV significantly.

OBJECTIVETo investigate the correlation between the HLA genes and pathogenesis of aplastic anemia (AA), so as to find the susceptible AA genes.

METHODSPolymerase chain reaction with specific sequence primers (PCR-SSP) method was used to detect the HLA typing of 50 AA patients and 183 normal healthy individuals as controls in Chinese Han population of northwestern plateau.

RESULTSThe frequency of HLA-A* 0201 (45.0%), B* 1501 (11.0%), B* 5501 (9.0%) and DRB1* 0901 (19.0%) gene frequences in AA patients were significantly higher than those in controls (Odds Ratio: OR=1.657, 2.138, 2.314 and 1.932, x2=4.882, 3.876, 3.863 and 4.473 (P<0.05). In contrast, A* 0301 gene frequency (4.0%) in AA was significantly lower than that in controls, OR=0.349, x2=4.154 (P<0.05). The male HLA-A* 0201 gene frequency was lower than that in female (38.2% vs 59.4%), and the difference was statistically significant (P<0.05). Concludsion: The HLA-A* 0201, B* 1501, B* 5501 and DRB1* 0901 genes may be considered as the risk markers while A* 0301 gene as a protective marker of AA, the HLA-A* 0201 also shows the sex differences.

Alleles ; Anemia, Aplastic ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; HLA-DRB1 Chains ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic

OBJECTIVETo investigate the correlation of immunologic thrombocytopenia(ITP) pathogenesis with the abnormal expression of IL-21, and to explore the association of high-dose dexamethasone (HD-DEX) treatment with the IL-21 expression.

METHODS26 newly diagnosed ITP patients and 24 healthy controls were enrolled in this study. The mononuclear cells and serum were obtain from density gradient centrifugation in the newly diagnosed ITP patients before HD-DXM treatment, and the samples of healthy controls were also used for assays. The protein and mRNA expression of IL-21 on peripheral blood mononuclear cells(MNC) were determined by flow cytometry and real-time reverse-transcription polymerase chain reaction. Plasma levels of IL-21, IFN-γ and IL-4 were determined by enzyme-linked immunoabsorbent assay (ELISA).

RESULTSIL-21 expression on mononuclear cells was significantly higher in ITP patients (13.07%) than that in normal controls (8.2%), the ratio of IL-21/GAPDH mRNA expression on MNC was significantly higher in ITP patients (9.524±0.97) than that in normal controls (3.701±0.60, P<0.01). After HD-DXM therapy, the ratio of IL-21/GAPDH mRNA decreased significantly (5.87±1.21) as compared with the level before treatment. Significantly high levels of serum IL-21, IFN-γ and lower IL-4 were found in ITP patients, as compared with healthy controls. Serum IL-21 and IFN-γ levels in ITP patients decreased significantly after HD-DXM administration (P<0.01), while post-treatment levels of IL-4 were increased significantly, compared with the levels before treatment (P<0.01).

CONCLUSIONTherapeutic effect of DXM on ITP associates with down-regalation of IL-21 expression. The increased expression of IL-21 involves in the pathogenesis of ITP.

Dexamethasone ; Flow Cytometry ; Humans ; Interleukin-4 ; Interleukins ; Leukocytes, Mononuclear ; Purpura, Thrombocytopenic, Idiopathic ; RNA, Messenger

This study was aimed to investigate the effect of salidroside on proliferation of bone marrow mesenchymal stem cells (MSC) and their secretion of stem cell factor (SCF). MSC were isolated and amplified in vitro via density gradient centrifugation and adherence screening method. MCS were identified by flow cytometry and osteogenic/adipogenic induction. The effects of salidroside on cell proliferation, cell cycle and the SCF secretion of MSC were detected by flow cytometry. The results showed that the salidroside could induce the proliferation of MSC, peaked at the concentration of 1.5 mg/ml and in a time-dependent manner (in 24 h, 48 h and 72 h). Salidroside at 1.5 mg/ml could more effectively increase the percentage of cells in S and G1/M phase. Co-cultured with salidroside at the concentration of 1.5 mg/ml for 48 h, the SCF and the expression levels of SCF mRNA in co-culture supernatant were both significantly increased (P < 0.01). It is concluded that salidroside in a range of certain concentration can obviously promote the proliferation of MSC and increase the expression and secretion of SCF.
Bone Marrow Cells ; cytology ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Glucosides ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Phenols ; pharmacology ; Stem Cell Factor ; secretion