PX-12 Promoting Apoptosis of Multiple Myeloma Cell Line H929 Induced by Bortezomib / 中国实验血液学杂志

OBJECTIVE@#To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib.@*METHODS@#MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H@*RESULTS@#MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G@*CONCLUSION@#PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.

Clinical Efficacy of EPOCH±R Followed by DICE±R Regimen for Primary Breast Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical efficacy and safety of EPOCH±R followed by DICE±R regimen for primary breast diffuse large B-cell lymphoma.</p><p><b>METHODS</b>Forty-three patients with primary breast diffuse large B-cell lymphoma were admitted in our hosptial from January 2000 to April 2016. Among them 24 patients were treated with CHOP±R regimen, 19 patients were treated with EPOCH±R followed by DICE±R regimen. The clinical efficacy, survival rate and adverse effects were observed and compared between them.</p><p><b>RESULTS</b>The complete rate in EPOCH±R followed by DICE±R regimen group was higher than that in the CHOP±R group (84.2% vs 70.8%), and the relapsed rate was lower in EPOCH±R followed by DICE±R regimen group than that in the CHOP±R group (6.25% vs 35.3%). Progression-free survival (PFS) and overall survival (OS) rates of 5 years after diagnosis in the EPOCH±R followed by DICE±R group were significantly higher as compared with that in CHOP±R group (PFS, 75% vs 47.4%, P=0.035; OS, 73.3% vs 45.2%, P= 0.043). Treatment-related hematologic adverse events were more serious in the EPOCH±R followed by DICE±R group(63.2% vs 25%). However, these adverse events were controlled and no treatment-related deaths were observed. Multivariate analysis showed that age (P=0.008; 95% CI, 0.026 to 0.579), radiotherapy (P=0.045; 95% CI, 1.028 to 14.719) and LDH level (P=0.007; 95% CI, 0.017 to 0.531) were independent prognostic factors for 5 year overall survival.</p><p><b>CONCLUSION</b>EPOCH±R followed by DICE±R regimen is an effective and safe treatment regimen for PB-DLBCL. Prognostic factors for survival are age, LDH level and radiotherapy.</p>

Application of lenalidomide in chronic lymphocytic leukemia / 中国实验血液学杂志

In recent years, the incidence of chronic lymphocytic leukemia (CLL) is increasing. Microenvironment and immune system play a key role in the pathogenesis of CLL. The immune system is aggravated by the use of chemotherapeutic agents, such as fludarabine and cyclophosphamide with rituximab(FCR) which are the current standards in frontline therapy. This leads to an increase of infection incidence in patients, resulting in a poor prognosis. The present situation was changed by lenalidomide. Recent studies indicated that lenalidomide monotherapy in treatment of refractory or relapsed CLL patients, the overall response rate(ORR) reached about 32%-47%, CR roughly was 7%-13%; when lenalidomide and rituximab were combined for treatment of refractory or relapsed CLL patients, the ORR reached about 53%-66%, CR about 12%-13%. Moreover, when lenalidomide and ofatumumab were combined, the efficacy is improved significantly and the adverse reactions are greatly reduced. The adverse reactions are neutrophilic granulocytopenia, thrombocytopenia, anemia, tumor lysis syndrome(TLS), tumor flare reaction(TFR) and venous thromboembolism(VTE). This review focuses on the related studies and the latest progress about lenalidomide in CLL.

Expression of TRAF-6,TAK1 and TGF-β mRNA in peripheral blood mononuclear cells of patients with diffuse large B cell lymphoma before and after chemotherapy / 中国实验血液学杂志

This study was purposed to detect the expression levels of TRAF6, TAK1 and TGF-β mRNA in peripheral blood mononuclear cell (PBMNC) of patients with diffuse large B cell lymphoma (DLBCL) before and after chemotherapy, and to explore the effect of chemotherapy on the activity of TRAF6/TAK1 signal pathway. The expression levels of TRAF-6, TAK1 and TGF-β mRNA in PBMNC of 38 patients with DLBCL were detected by using the quantitative real time PCR before treatment or after two cycles of chemotherapy, 12 healthy people were served as the control. The results showed that the expression levels of TRAF-6, TAK1 and TGF-β mRNA in PBMNC of DLBCL patients' were higher than those in healthy people. Before treatment, the expression levels of TRAF-6 and TAK1 mRNA had no significant difference as compared with healthy people (P > 0.05); after chemotherapy, the expression levels of these two genes significantly increased, and the differences both had statistically significant as compared with healthy people (P < 0.05); meanwhile the increased expression levels of these two genes after chemotherapy had statistically significant difference as compared with levels before treatment (P < 0.05) , and those expression levels were positively correlated. While the expression level of TGF-β mRNA decreased after chemotherapy as compared with level before treatment, and the differences had statistically significantse(P < 0.05). It is concluded that the activity of TRF6/TAK1 signal pathways in PBMNC of DLBCL patients' significantly increases after chemotherapy, while the expression level of TGF-β mRNA after chemotherapy is abviously lower than level before treatment.

Clinical study of COAD-B regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy, adverse events and long-term survival of cyclophosphamide, vindesine, cytarabine, dexamethasone and bleomycin (COAD-B) regimen for relapsed and refractory non-Hodgkin lymphoma (NHL).</p><p><b>METHODS</b>Eighty six patients diagnosed with relapsed or refractory NHL were included in our study from January 2007 to January 2013. The chemotherapy regimen was COAD-B, the therapeutic efficacy was evaluated every 2 courses. Once the stable disease (SD) or progress of the disease (PD) achieved, the patients would switch to other second-line regimens.</p><p><b>RESULTS</b>The overall response rate (ORR) was 67.4%, median remission duration was 13 months (3-51 months); 1-,2- and 4-year overall survival (OS) rates were 75.4%, 56.8% and 40.0%, respectively; 1-, 2- and 4-year progression-free survival (PFS) rates were 50.3%, 39.4% and 27.5%, respectively. The main adverse reaction of patients was myelosuppression. The response to chemotherapy and long- term survival of the relapsed patients were significantly better than that of the refractory ones, and the difference had statistical significance.</p><p><b>CONCLUSION</b>COAD-B could be the salvage regimen for relapsed and refractory NHL.</p>

Clinical significance of dynamic monitoring of thymic recent output function in different stages of treatment in patients with diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To detect the changes of naive T cell level of thymic recent output at different stages of treatment in patients with diffuse large B-cell lymphoma (DLBCL), thereby to evaluate the relationship of thymic recent output function with prognosis and the impact of chemotherapy on the potential of immunological recovery.</p><p><b>METHODS</b>The levels of T-cell receptor rearrangement excision circles (TREC) in DNA of peripheral blood mononuclear cells (PBMNC) from 30 DLBCL patients were monitored before, during, until 3 months and 6 months after chemotherapy by real-time PCR (TaqMan), and TREC-level was detected according to the number of CD3 positive(CD3(+)) cells. Twelve normal individuals who matched in age were served as controls.</p><p><b>RESULTS</b>There was a dramatic reduction of TREC values in all DLBCL patients among which TREC values in germinal center B-cell-like-DLBCL (GCB-DLBCL) were higher than those in non-GCB-DLBCL, as compared with TREC values of normal individual in peripheral blood. The mean values of TREC were 0.91 ± 0.15/1000 PBMNCs and (1.22 ± 0.69)/1000 CD3(+) cells in GCB-DLBCL, (0.43 ± 0.29)/1000 PBMNCs and (0.64 ± 0.44)/1000 CD3(+) cells in non-GCB-DLBCL before chemotherapy. TREC values were significantly associated with lower international prognostic index (IPI) grade (r = -0.441, P = 0.015). TREC-level in DLBCL patients was further decreased after chemotherapy, and reached to the lowest level after the 6th cycle of chemotherapy, and during the corresponding period, the mean values of TREC were (0.63 ± 0.34)/1000 PBMNCs and (0.89 ± 0.65)/1000 CD3(+)cells in GCB-DLBCL, (0.19 ± 0.11)/1000 PBMNCs and (0.27 ± 0.25)/1000 CD3(+) cells in non-GCB-DLBCL. TREC-level began to rise obviously 3 months after the last cycle of chemotherapy in most of the DLBCL patients, and came close to normal level in five cases of patients 6 months after the last cycle of chemotherapy.</p><p><b>CONCLUSIONS</b>Thymic recent output function was impaired severely in DLBCL patients. There was an important relationship between thymic recent output function before chemotherapy and prognosis, and chemotherapy had influenced the potential of immunological recovery.</p>

Hyperthermia increases the sensitivity of RPMI 8226 cells to adriamycin / 中国实验血液学杂志

This study was purposed to explore the effect of hyperthermia on sensitivity of multiple myeloma cells RPMI 8226 to adriamycin (ADM) and its mechanism. The working concentration of ADM against RPMI 8226 cells was defined by MTT assay. RPMI 8226 cells were divided into 4 groups: control group, hyperthermia (42°C) group, chemotherapy (ADM) group and combination group (42°C + ADM), the survival rate of RPMI 8226 cells in 4 groups was detected by trypan blue exclusion, the inhibitory effect of hyperthermia on proliferation of RPMI 8226 cells was detected by MTT assay, the cell cycle distribution, apoptosis rate of cells, intracellular ADM concentration and P-gp expression level were measured by flow cytometry. The 1/4 IC(50) of ADM was defined as the working concentration in the experiment. The results indicated that the hyperthermia promoted the entering the cells from in G(0)/G(1) phase into S and G(2)/M phases, the expression of P-gp protein on cells in hyperthermia and combination groups was down-regulated, the intracellular ADM concentration in combination group obviously increased. It is concluded that the hyperthermia combined with ADM obviously enhance the inhibitory effect on proliferation of RPMI 8226 cells. The hyperthermia increases the sensitivity of RPMI 8226 cells to chemotherapy through down-regulating the expression of P-gp protein on cells and increasing the intracellular ADM concentration.

The expression of microRNA-155 and microRNA-146a and its' clinical value in chronic lymphoproliferative disorders / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of microRNA-155 and microRNA-146a in the CD19(+) B cells of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and to analyze its clinical significance.</p><p><b>METHODS</b>Peripheral blood (PB) (78 cases) and bone marrow (BM) samples (9 cases) from 53 CLL patients, 13 MCL patients, 19 SMZL patients, and 12 healthy donors were collected. Mononuclear cells were isolated and B cells were purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and microRNAs expression were measured using the TaqMan microRNA quantitative PCR. The results combined with the clinic data of patients were analysed.</p><p><b>RESULTS</b>(1) The expression of microRNA-155 in CLL (4.49 ± 0.83) was significantly higher than in MCL (3.83 ± 0.45) and SMZL (3.80 ± 0.61) (P < 0.05); (2) The level of microRNA-146a in SMZL (3.81 ± 0.59) was significantly higher than in CLL (2.58 ± 0.90) and MCL (2.27 ± 0.88) (P < 0.01); (3) The level of microRNA-155 was significantly higher in IgVH unmutated patients than in mutated patients in CLL (P = 0.012); (4) The microRNAs expression had no statistical difference between two prognostic groups in CLL.</p><p><b>CONCLUSION</b>(1) The expression of microRNA-155 and microRNA-146a is different in malignant lymphoproliferative disorders (LPD); (2) Deregulation of the microRNAs expression might play a critical role in the pathogenesis and prognosis in the LPD.</p>

The efficacy of high-dose cytarabine for patients with t(8;21) AML and with normal karyotype AML / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of high-dose cytarabine (HD-Ara-C) based chemotherapy for post-remission treatment in patients with t(8;21) (q22;q22) AML-M2 and those with normal karyotype AML-M2.</p><p><b>METHODS</b>AML-M2 patients were grouped into with (21 cases) or without (23 cases) t(8;21) (q22;q22) karyotype groups. After achieved remission by induction therapy, all patients received four cycles of HD-Ara-C (3 mg/m2 per 12 hours by three-hour infusion day 1 to day 3) with either mitoxantrone (7 mg m(-2) d(-1)) or aclarubicin (30 mg m(-2) d(-1)) or etoposide (70 mg m(-2) d(-1)) for 3d as post-remission treatment.</p><p><b>RESULTS</b>Relapse rate in the t(8;21) and the normal karyotype groups was 29% and 57% respectively (P<0.05); 3 year disease-free survival (DFS) rate was 71% and 43% respectively (P < 0.05). and 3 year over-all survival (OS) rate was 76% and 65% respectively (P >0.05).</p><p><b>CONCLUSION</b>Four cycles of high-dose cytarabine based combination chemotherapy as post-remission treatment improves long-term disease-free survival in patients with t(8;21) (q22;q22) AML-M2.</p>

Comparative characterization of mesenchymal stem cells from human umbilical cord tissue and bone marrow / 中国实验血液学杂志

This study was purposed to compare the biological characteristics of umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The frequency of successful isolation, cell yield, colony-forming units-fibroblastics (CFU-F), proliferation capacity, immunophenotype and multi-differentiation potentials of UC-MSCs and BM-MSCs were determined by limiting dilution assay, flow cytometry, invert microscopy, RT-PCR and so on, the determined results were compared. The results showed that MSCs were successfully isolated from all the 36 portion of UC tissue and 8 portion of BM. Although the mean number of nucleated cells isolated from UC tissue was significantly lower than that from BMs (1 x 10(6)/cm vs 5.5 x 10(7)/ml) (p=0.0002), no significant differences of the yield of adherent cells were observed (8.6 x 10(5)/cm vs 8.4 x 10(5)/ml) (p>0.05). UC-MSCs shared the most of the characteristic of BM-MSC, including fibroblastic-like morphology, typical immunophenotype, cell cycle status, adipogenic and osteogenic differentiation potentials. However, the CFU-F frequency was higher in UC (1:1609+/-0.18) than that in BM (1:35700+/-0.01) (p<0.05). Furthermore, the proliferation capacity of UC-MSCs was higher than that of BM-MSCs; the expressions of CD106 and HLA-class I in UC-MSCs were lower than those in BM-MSCs (p<0.05). It is concluded that the cell yield and most biological characteristics of UC-MSCs are similar to BM-MSCs, but UC-MSCs possess the higher proliferation capacity, and the lower expression of HLA-class I and HLA-DR as compared with BM-MSCs, therefore the human umbilical cord tissue may be considered as a promising alternative to bone marrow as a source of MSCs.

Application of all-trans retinoic acid combining chemotherapy and As4S4 in the maintenance treatment of patients with acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of all-trans retinoic acid (ATRA) combining chemotherapy and As4S4 with ATRA combining chemotherapy for the maintenance treatment of patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Sixty patients with APL induced to complete remission by ATRA and consolidated by chemotherapy were randomly divided into two groups. Thirty patients as As4S4 group received ATRA + As4S4 + chemotherapy, and another thirty patients as non-As4S4 group were treated only with ATRA + chemotherapy as maintenance therapy. The therapeutic effects, side effects and PML-RARalpha gene expression were analyzed.</p><p><b>RESULTS</b>The three-year continuous complete remission (CCR) rate was 90.0% for As4S4 group and 61.1% for non-As4S4 group, the difference being statistically significant. Significant difference was also found in the positive rate of PML-RARalpha fusion gene between the two groups. The side effects were mild.</p><p><b>CONCLUSION</b>APL patients in maintenance therapy with ATRA + 6-MP + MTX + As4S4 can obtain a higher CCR.</p>

MEKK2 regulates the production of interleukin 2 / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the role of MEKK2 on the production of IL-2 in Jurkat cells stimulated by PHA/anti-CD28 antibody.</p><p><b>METHODS</b>The MEKK2 and JNK kinase activities were measured in both dominant negative MEKK2 Jurkat (dnMEKK2 Jurkat) cells and parental Jurkat cells. The AP(1) and IL-2 promotor activities were measured by luciferase activity assay. The IL-2 mRNA and protein were detected by RT-PCR and Western blot.</p><p><b>RESULTS</b>After stimulation by PHA/anti-CD28, JNK was activated in parental Jurkat cells but not in dnMEKK2 Jurkat cells. The luciferase report gene activities of AP1 and IL-2 promotors were increased by 4- and 5-folds in parental cells whereas only by 1 fold in dnMEKK2 Jurkat cells. The level of IL-2 mRNA and IL-2 protein were increased in parental Jurkat cells but not in dnMEKK2 Jurkat cells.</p><p><b>CONCLUSION</b>MEKK2 plays an important role on the production of IL-2 in Jurkat cell stimulated with PHA/anti-CD28 antibody. It is a potential drug target for the treatment of GVHD and autoimmune disease.</p>