AIM To gain insight into the biochemical mechanisms of Topotecan induced apoptosis in leukemia cells. METHODS The cytotoxic effect of Topotecan on HL 60 cells was measured by using MTT assay; Topotecan induced apoptosis in HL 60 cells was identified by morphological analysis, DNA agarose gel electropheresis and Annexin V FITC staining; correlation between Topotecan mediated apoptosis and caspase activation was investigated by caspase 8 or caspase 3 inhibitor. RESULTS After incubated with 0 1 ?mol?L -1 TPT for 8,12 and 16 h, survival rate in HL 60 cells significantly reduced to 62%?12%( P

Objective To observe the efficacy and main complications of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for 76 patients with hematopoietic malignancies.Methods From September 2001 to March 2007,76 patients received allo-HSCT in Department of Hematology,Xijing Hospital,Fourth Military Medical University.All cases included 24 acute myeloid leukemia(AML),15 acute lymphocytic leukemia(ALL)and 34 chronic myelogenous leukemia(CML)and 3 T cell lymphoma/leukemia.Donors were HLA-identical sibling(n=57),1 locus mismatched sibling(n=3),HLA-matched unrelated volunteer(n=9)and haplo-identical sibling(n=7).Conditioning regimen consisted of busulphan-cyclophosphamide or cyclophosphamide and total body irradiation plus Ara-c/VP-16.Graft versus-host disease prophylaxis was the standard methotrexate and cyclosporine combination.Anti-human thymocyte immunoglobulin(ATG)and CD25 monoclonal antibody was given in unrelated donor and haplo-identical HSCT.Results Totally 73 patients got sustained engraftment.Acute GVHD and chronic GVHD were found in 18/73(24.7%)and 24/73(32.9%)patients,respectively.Severe veno-occlusive disease occurred in 2 cases.Pure red cell aplasia was found in 5 patients with major ABO mismatched HSCT.With a follow-up of 3 to 76 months,43/76(56.6%))patients were still alive and 33/76(43.4%)died from leukemia relapse or transplantation-related complications.Conclusion Allogeneic heamatopoietic stem cell transplantation is an effective therapy for leukemia,especially in CML-chronic period and acute leukemia in complete remission,but there is high rate of relapse in patients with high-risk and refractory status before transplantation.

Objective To observe the changes and the mechanism of bcl-6 expression in K562 cells inducing differentiation along different Myelocyte-lineage cells,and to investigate the relationship between expression of bcl-6 and directional differentiation of K562 cells.Methods Models of K562 cells inducing differentiation along megakaryocyte-lineage,erythrocyte-lineage and macrophagocyte- lineage were established with inducers TPA(tetradecanoylphorbol 13-acetate),Hu(hydrozyurea)and HMBA(hexamethylene bisacet- amide)respectively,Western blot assay was applied to detect the expression of bcl-6 in K562 cells before and after the induction.Mean- while,PCR,cloning and direct DNA sequencing were used to identify mutations in the 5'regulatory region of bcl-6 in K.562 cells induced with TPA.Results Up-regulation of bcl-6 expression was found only in K562 cells inducing differentiation along megakaryocyte-line- age,and mutation of noncoding regulatory region of bcl-6 gene was not found.Conclusions bcl - 6 may be the key gene to regulate K.562 cells directional differentiation along different myelocyte-lineage ceils,the up-regulation of bcl-6 expression could play an important role in K562 cells inducing differentiation to megakaryocydte-lineage,and the change of bcl-6 expression might be not related with the mutation of the gene's 5'regulatory region.

Objective To explore the value of applying multiple disciplinary team (MDT) in the clinical practice teaching of lymphoma. Methods 5-year program clinical medicine undergraduate students of 2012 were divided into experimental and control group randomly, with 30 cases in each group. The ex-perimental group received MDT in clinical teaching through MDT conference and cases analysis. The control group received conventional teaching mainly by smal class presentation and ward round . The effect of teaching was evaluated by examination and questionnaire. The data were analyzed through t-test and chi-square test by SPSS 20.0 software. Results The results showed the students' scores of the theory knowledge test of two groups were similar to each other, but the scores of discussional topic and clinical cases analysis were higher in experimental group than control group and statistically difference [(16.5 ±2.3)vs. (10.5 ±1.8);(37.5±2.5) vs.(27.5±1.8)], (P=0.000), and the final score of two groups showed statistically difference (93.5± 5.2 vs. 76.0 ±6.2) (P=0.000). Meanwhile, questionnaire survey of satisfaction showed that 27 students of experimental group (90.0%) were interested in this new teaching model, 29 students (96.7%) believed it im-proved understanding and memory to the process of lymphoma diagnosis and treatment, 25 students (83.3%) believed it could improved the ablility to diagnose and differential diagnose lymphoma and expanded their clinical view. 28 students (93.3%) had consolidated clinical thinking, and 26 students (86.7%) improved negotiation with patients. All issues were significantly better than control group (P<0.05). Conclusions The clinical teaching model innovation based on MDT could help medical students use the cross-discipinary interviewing and make optimal treatment plan for patients. It is conducive to the cultivation of their diagnosis, differential diagnosis and clinical thinking ability, which is worthy of promotion in hematological clinical teaching.

Objective To describe the demographic and clinical characteristics of patients with the diagnosis of multiple myeloma(MM)and to analyse the outcome of difierent regimens for the treatment of MM.Methods The study reviewed 332 MM cases diagnosed within the period from January 1,2002 to December 31,2002.These patients were tracked via their records to a total period of three years.Results First-line treatment:Totally 332 patients were included,among them 325(97.9%)patients received chemotherapy and 7(2.1%)patients received stem cell transplantation(SCT);Second-line treatment:197 patients were included,among them 190(96.5%)patients received chemotherapy and 7(3.6%)patients received SCT;Third-line treatment:92 patients were included,among them 88(95.7%)patients received chemotherapy and 4(4.4%)patients received SCT.Major adverse effects were follows:severe infection 19.3%,severe anaemia 19.3%,phlebothrombosis 1.2%,thrombocytopenia 16.9%,fever associated with neutropenia 18.1%.Conclusions Some curative effects can be achieved by using traditional treatment plans to treat patients suffering from MM,but new methods are expected to improve the prognosis.

Objective To investigate the expression of bone marrow γ-H2AX in the patients with multiple myeloma(MM) and its correlation with the prognosis.Methods The patients with newly diagnosed MM in this hospital were selected as the case group,and the patients with non-hemopoietic system tumor without obvious morphological abnormalities by bone marrow smear and biopsy served as the control group.The immunohistochemistry was adopted to detect the expression level of bone marrow γ-H2AX in the cases group and control group,the image-Pro Plus(IPP) semiquantitative analysis was performed.The expression differences were compared between the two groups,moreover the case group was re-divided into the strong expression group and weak expression group according to γ-H2AX expression level.Then the relation ship between γ-H2AX expression level and the prognosis in the patients with MM.Results The bone marrow γ-H2AX expression level in the case group was significantly higher than that in the control group (P＜0.05);the level of γ-H2AX expression in the strong expression group was significantly stronger than that in the weak expression group (P＜0.05).Conclusion The level of γ-H2AX expression was higher among MM patients,and the over expression of γ-H2AX predicts the shorter survival time.

Drug Delivery Systems ; Humans ; Lymphoma ; drug therapy ; United States

Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.