Research Progress of Cancer-associated Fibroblasts in Hematolo- gic Malignancies --Review / 中国实验血液学杂志

Cancer-associated fibroblasts （CAF） are a key component of the tumor microenvironment, which can secrete a variety of cytokines, chemokines and growth factors, directly and indirectly support cancer cells, also alter the immune cellular environment by inhibiting the activity of immune effector cells and recruiting immunosuppressive cells, thereby allowing cancer cells to evade immune surveillance. CAF has been proven to be associated with the development, progression, and poor prognosis of solid tumors. However, the role of CAF in hematological malignancies is still unclear. This article reviews the research progress of CAF in hematological malignancies.

Recent Research Progress of Extramedullary Plasmacytoma --Review / 中国实验血液学杂志

Extramedullary plasma cell tumor (EMP) is a kind of plasma cell tumor, and its pathogenesis is not completely clear. According to whether it is independent of myeloma disease, it can be divided into primary and secondary EMP, which have different biological and clinical characteristics. Primary EMP has low invasion, fewer cytogenetic and molecular genetic abnormalities and good prognosis, and surgery and / or radiotherapy are the mainly treatments. Secondary EMP, as the extramedullary invasive progression of multiple myeloma (MM), is often accompanied by high-risk cellular and molecular genetic abnormalities and poor prognosis, chemotherapy, immunotherapy and hematopoietic stem cell transplantation are the mainly treatment. This paper reviews the latest research progress of EMP in the pathogenesis, cytogenetics molecular genetics and treatment, so as to provide reference for clinical work.

The Relationship between Body Mass Index and Adult Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analysis the relationship between different BMI (body mass index) and the clinical characteristics, laboratory examination indexes of newly diagnosed adult patients with acute myeloid leukemia (AML), so as to investigate the effects of BMI to the efficacy of first induction chemotherapy.@*METHODS@#The clinical data of 145 newly diagnosed adult AML patients treated in the First Hospital of Lanzhou University from August 2015 to August 2019 were retrospective analyzed. According to the guidelines for prevention and control of overweight and obesity in Chinese adults, the BMI (kg/m@*RESULTS@#Among the 145 newly diagnosed adult AML patients, there were 71 males and 74 females. The median age was 50 years old(range 18 to 82 years old). There were 21 patients in underweight group (14.5%), 79 patients in normal weight group (54.5%), and 45 patients in overweight and obese group (31.0%). The patients with higher BMI level showed the older in age（P=0.018）. There were significant differences in sex between the patients in each group(P=0.035). In overweight and obese patients, the number of male was significantly higher than female. There were no statistical differences in AML classification, comorbidities(Diabetes, hypertension, coronary heart disease), hospital days, whether secondary AML and FLT3 gene mutation among the patients in different BMI groups. There were significant differences in TG of the patients in the different groups, the overweight and obese patients were higher (P=0.007). There were no significant differences in WBC and Hb counts, ALB, TC, HDL, LDL, or LDH between the patients in each BMI group at newly diagnosed. The complete remission rate of the patients in the low body mass group or overweight and obese group were lower than that in the normal body weight group (P=0.035). The rate of documented infection during the first induction chemotherapy were significantly higher for the patients in low body mass group than those in normal weight group or overweight and obese group (P=0.038). There was no statistical difference in chemotherapy regimens, the number of chemotherapy until CR, febrile neutropenia, bleeding, and the time of neutropenia, liver and kidney toxicity among each BMI group. Multivariate analysis showed that overweight and obese (P=0.012) , FLT3 mutation (P=0.015) were the risk factors affecting the CR rate of the patients. And the patients with secondary AML, high-risk type, and newly diagnosed WBC ≥50×10@*CONCLUSION@#In newly diagnosed adult patients with AML, low body mass, overweight and obesity, and FLT3 mutations were the factors reducing the early efficacy of AML patients. There were more adverse reactions induced by chemotherapy in the low body mass group. Therefore, inappropriate BMI level can be a risk factor for assessing the prognosis of adults with newly diagnosed AML.

Expression and Prognostic Value of Metabolism-related Genes in Pediatric Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression and prognostic value of metabolism-related genes in pediatric acute lymphoblastic leukemia (ALL), and explore the potential prognostic biomarkers or therapeutic targets.@*METHODS@#Transcriptome data from 84 children with B-cell ALL at the time of diagnosis and prior to any treatment were used to analyze the differential gene expression. A prognostic scoring system based on the expression of the metabolism-related genes was constructed using Cox and Lasso regression methods. The prognostic value of the scoring system was further assessed by multivariate Cox regression analysis. Gene set enrichment analysis was carried out by using GSEA software.@*RESULTS@#Among the 933 metabolism-related genes, 14 up-regulated genes and 17 down-regulated genes were identified as differentially expressed genes. In addition, 8 up-regulated genes (ASS1, CKM, PTGES, ADCY5, HNMT, PHGDH, CYP4F3, AADAT) and 4 down-regulated genes (GDA, DHRS9, IDO2, UGT2B4) were selected to establish a novel prognostic scoring system. Patients in the high-risk group showed poorer survival significantly than patients in the low-risk group (P<0.05). The prognostic scoring system was still shown to be an independent prognostic factor for the survival of children with ALL after the clinical characteristics, such as gender, age, white blood cell count at initial diagnosis, cytogenetics and molecular genetics were included (HR=8.906, 95%CI: 3.114-25.470). GSEA results showed that 6 metabolism-related pathways (amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, glyoxylate and dicarboxylate metabolism, pyrimidine metabolism, selenoamino acid metabolism) were enriched in the high-risk group.@*CONCLUSION@#The abnormal metabolism-related gene expression is associated with the clinical outcome of children with ALL, and these results provide potential novel prognostic biomarkers and treatment targets for pediatric ALL.

Distribution and Drug Sensitivity of Pathogens Causing Nosocomial Infection in Patients with Hematological Granulocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution and drug resistance of nosocomial infection pathogens in AL patients with hematological agranulocytosis, so as to provide evidence for the clinical rational use of antibiotics.@*METHODS@#Pathogenic data of 504 hospitalized patients with agranulocytosis caused by nosocomial infection in the Department of Hematology, the First Hospital of Lanzhou University from May 2015 to May 2018 were collected and retrospectively analyzed for the distribution of pathogenic bacteria and the results of drug susceptibility.@*RESULTS@#The isolated pathogenic bacteria strains amounted to 184, out of which, 168 strains (91.3%) orginated from the patients with acute leukemia, while 16 strains (8.7%) originated from the patients with non-acute leukemia. The positive samples mainly originated from blood stream, the isolated bacteria from which were 81 straims (44%); then originated from sputam and pharynx swabs, from which isolated bacteria amounted to 54 strains (29.3%) and 35 strains (19%) respectively. In the pathogenic bacteria, the Gram-negative bacteria amounted to 126 strains accounting for 68.46%, out of which the most commond bacteria strains were Klebseilla pneumoniae, cscherichia coli and Pseudomonas aeruginosa; the Gram positive bocteria amounted to 23 strains accounting for 12.5%, mainly staphy lococeus anreus, and Staphylococcus epitermidis; the fungi amounted to 35 strains accounting for 19.02%, mainly Candida albicans. The detection rates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases (ESBLs) were 40.0% and 22.2%, respectively. They were 100% sensitive to amikacin and 27.8% resistant to carbapenems. Klebsiella pneumoniae had the highest sensitivity to amikacin, 94.44% to ampicillin, 97.22% to carbapenems and 100% sensitive to ammonia. Their penicillin-resistance rate was the highest, up to 80%; Pseudomonas aeruginosa was sensitive to the antibiotics (＞80%）. Methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were detected in Gram-positive bacteria. The susceptibility rate of main Gram-positive bacteria to vancomycin and linezolid was 100%, and they were 100% resistant to penicillin.@*CONCLUSION@#Gram-negative bacteria are the main pathogens of nosocomial infection in patients with hematological agranulocytosis. Pathogens have different resistance to antimicrobial agents. It is important to know the distribution and susceptibility of common pathogens for rational selection of antimicrobial agents and control of nosocomial infection.

Clinical Analysis of Serum Calcium Level in 86 Cases of Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the serum calcium level in 86 patients with newly diagnosed multiple myeloma (MM) and its correlation with clinical features.@*METHODS@#The clinical data of 86 patients with newly diagnosed multiple myeloma in our hospital from 2009 to 2016 were retrospectively analyed. Clinical data of sex, age, hemoglobin, albumin, globulin, creatinine, uric acid, serum phosphorus, β2-microglobulin, immunophenotyping and disease staging were collected. After the serum calcium level was corrected, the patients were grouped into low serum calcium (2.60 mmol/L). The correlation between the clinical characteristics and the serum calcium level was analysed, the clinical characteristics between the low and non-low calcium group were compared.@*RESULTS@#The number of cases in low, normal and high serum cnlcium groups before correction was 58 (67.4%), 18 (20.9%) and 10 (11.6%) respactively, while the number of cases in 3 group after correction was 34 (39.5%), 36 (41.9%) and 16 (18.6%) respectively. The age, globulin, creatinine, uric acid and serum phosphorus levels were positively correlated with serum calcium level in patients with multiple myeloma, while the sex, hemoglobin,albumin and β2-microglobulin levels did not correlated with serum calcium level. There was significant difference in the age, globulin, creatinine and serum phosphorus between low calcium and non-low calcium group (P0.05).@*CONCLUSION@#Multiple myeloma patients suffered from both hypercalcemia and hypocalcemia, and the incidence of hypocalcemia is not low. The levels of serum calcium in patients with multiple myeloma correlate with age, globulin, creatinine, uric acid, serum phosphorus level and other factors, thus it is necessary to correct the level of ionized calcium with physiological activity.

Values of Different Prognostical Score Systems in Evaluation of Clinical Efficacy for Patients with Newly Diagnosed Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the values of 4 prognostic score systems in evaluation of clinical effecacy for patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatnib mesylate (IM) and the relationship between 4 prognostic score systems and deep molecular response (MR4.5).@*METHODS@#The clinical data of 240 CML-CP patients treated with imatinib mesylate in our hospital between Janunay 2008 and December 2017 were analyzed retrospecively. The risk was stratified according to 4 prognostic score systems, the relationship between the 4 prognostic score systems and 3-month early molecular response (3M-EMR), 6 month complete cytogenetic response (6M-CCyR), 12-month major molecular response (12M-MMR) as well as the correlation of the 4 prognostic score systems with deep molecalar response were analyzed.@*RESULTS@#At the end of treatment for 3 months, the EMR was evaluated for 219 patients, among them 164 (74.9%) patients achieved 3M-EMR; at the end of treatment for 6 months, CCyR was evaluated for 180 pathsents, among them 130 (72.2%) patients achicved 6M-CCyR; at the end of treatment for 12 months, the MMR was evaluated for 111 patients, among them 60 (54.1%) patients achieved 12M-MMR. Compared with the high-risk group, the treatment response to IM in the low-risk group (including the low-risk group and the intermediate-risk group) was better. There was significant difference in 3M-EMR according to Sokal score and ELTS score (P＜0.05), and there was significant difference in 12M-MMR according to EUTOS score and ELTS score (P＜0.05). Logistic regression analysis revealed Sokal score (HR=0.69, 95%CI：0.22-1.37, P＜0.05) and 3M-EMR (HR=0.47, 95%CI：0.28-0.84, P＜0.01) independently related with MR4.5, The combination of Sokal score, especially the low risk with 3M-EMR much more can predict MR4.5 (HR=0.42, 95%CI=0.21-0.82, P＜0.01).@*CONCLUSION@#There is a remarkable clinical efficacy of imatinib mesylate on CML-CP patients, moreover, low risk group has a better therapeutic response. Both Sokal score and ELTS score evaluate 3M-EMR better, both EUTOS score and ELTS score evaluate 12M-MMR better. The combination of low risk in Sokal score with 3M-EMR much more can predict MR4.5. The results of this study provide the reference basis for evaluating the clinical therapentic efficacy and timely modifying the therapeutic regimens for CML patients, also possess the reference value for predicting the MR4.5.

Effects of Tcd A on Rho GTPases and the Cytoskeleton of Leukemia Cell Line K562 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of clostridium difficile toxin A(TcdA) on the Rho GTPases and the cytoskeleton in K562 cells.</p><p><b>METHODS</b>K562 cells were cultured in vitro with different concentration of TcdA.The effect of TcdA proliferation of cells was detected by MTT method after the K562 cells were stimulated with TcdA for 24,48 and 72h; the expression of cdc42, RhoA, Rac1 mRNA was assessed by RT-PCR; the changes of the microtubule, the microfilament were observed by confocal laser scanning microscopy.</p><p><b>RESULTS</b>The proliferation of K562 cells was inhibited after exposure to TcdA for 24, 48 and 72h, and the inhibitory rate was 47.67% in the treatment for 48 h. the cdc42，RhoA and Rac1 mRNA expressions in the experimental groups decreased after treated with TcdA(P<0.05), which positively correlated with concentration of TcdA. Also, the microfilament decreased ,which was observed by confocal laser scanning microscopy.</p><p><b>CONCLUSION</b>TcdA inhibites K562 cell proliferation and induces apoptosis, TcdA can change the cytoskeleton structure through the cytoskeletal protein genes cdc42 and RhoA, Rac1 mRNA expression,. It is related with cell microfilament content decreasing.</p>

Effect of Icaritin on K562 Cell Proliferation and Intracellular Reactive Oxygen Species / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of icaritin (ICT) on proliferation of K562 cells and reactive oxygen species (ROS) in patients with chronic myeloid leukemia (CML).</p><p><b>METHODS</b>MTT assay was used to detect the effect of ICT on the proliferation of K562 cells. Flow cytometry was used to detect the apoptosis of K562 cells and intracellular ROS level. The expression of PARP protein was detected by Western blot.</p><p><b>RESULTS</b>ICT obviously inhibited the proliferation of K562 cells and induced their apoptosis, the expression of PARP protein was enhanced, and the intracellular ROS increased significantly.</p><p><b>CONCLUSION</b>The ICT showes the inhibitory effects on proliferation and apoptosis-inducing effects on K562 cells, and thier mechanism relats with the increase of reactive oxygen species in the cells.</p>

Clinical Characteristics of 223 Chinese Patients with Hemophilia in A Medical Center of Gansu Province in China / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, diagonsis and treatment of patients with hemophilia in Gansu province of China.</p><p><b>METHODS</b>The clinical data of 223 cases of hemophilia in our center between January 2010 and May 2015 were collected and analyzed retrospectively, these 223 cases of hemophilia were from 14 cities in Gansu and neighboring provinces, including 203 cases of hemophili A (HA) and 20 cases of hemophili B (HB), among them 222 cases were male, only 1 female(HA), 177 cases were from Rural areas (79.4%).</p><p><b>RESULTS</b>The median age of first bleeding was 2 years old, and the average age of confirmed as hemophilia was 5.6±6.5 years, the delayed time of diagnoses of HA and HB was 2.50±4.91 and 2.07±4.76 years, respetively, among all the patients 168 caese complicated with joint hemorrhage (75.3%), 123 cases with joint deformities (55.2%). 91.6% of the patients were treated according to demand, the HBV and HCV infection rates were 1.7% and 6.2% respectively. The first-visited hospital of 86.9% patients was hospitalized below 3 grade of level, only 15.9% of these patients were considered to diagnose as hemophili.</p><p><b>CONCLUSION</b>The accurate level of diagnosis rate for hemophiliacs in Gansu province is low, the delay time of diagnosis is longer, the ratios of complicated joint hemorrhage, total accumulative joint deformity were high, HCV infection rate is also high.</p>

Construction of Eukaryotic Expression Vector of siRNA Specific for BCR/ABL Fusion Gene and Its Effects on K562 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To construct eukaryotic expression vector of siRNA specific for BCR/ABL and to investigate the effect of recombinant plasmid on BCR/ABL and P210 protein expression in K562 cells.</p><p><b>METHODS</b>siRNA(small interfering RNA)was designed according to the Tuschl's principle of Ai-based medicine, and was converted into cDNA coding expression of shRNA(small hairpin RNAs)of siRNA for BCR/ABL fusion gene. The cDNA was synthesized and inserted into plasmid pTER. The pTER117 and pTER363 of recombinant plasmid being eukaryotic expression vector was controlled by the H1 promoter of RNA polymerase III, and identified by the restriction map and the sequence analysis. The recombinant plasmid did not only have the screening resisting antibiotics, its expression but also are induced by tetracycline (tet). After steadily transfection into K562 cells by Lipofectamine, their positive mono-cell clones being resistant to Zeocin were isolated. TaqMan real-time quantitative RT-PCR (RQ-PCR) and Western blot respectively detected expression of BCR/ABL mRNA and P210 protein. Trypaum blue dying was used to analyze the proliferation of K562 cells. Cell apoptosis was observed by flow cytometer.</p><p><b>RESULTS</b>the recombinant plasmid was steadily transfected into K562 cells by Lipofectamine 2000, Their positive mono-cell clones being resistant to Zeocin were isolated. The proliferation of K562 cells were remarkably inhibited by the recombinant plasmid induced gene expression by tetracycline. Tetracycline induced its expression for 48 h and 72 h. pTER117, pTER363 decreased the mRNA level of BCR/ABL 90%, 82% and 91.5%, 84%, respectively, P210 protein were almost measured in K562 cells. FCM analysis showed that the recombinant plasmid induced apoptosis in K562 cells, the apoptosis rate were respectively 34.4%, 58.1% in K562 cells treated by pTER117 for 48 h and 72 h, apoptosis rate were 31.8%, 54.6% by pTER363, but the control groups did not show these effects on K562 cells.</p><p><b>CONCLUSION</b>The siRNA eukaryotic expression vector against BCR/ABL mRNA has been successfully conctructed,and effectively inhibits the expression of BCR/ABL in K562 cells, inhibite cell growth and induce cell apoptosis.</p>

Therapy-related Virus Reactivation in Lymphoma Patients with Hepatitis B Virus Infection--Review / 中国实验血液学杂志

The incidence of HBV infection in lymphoma patients is much higher than that in the general normal population. HBV reactivation caused by treatment is one of the common complications in considerable amount of lymphoma patients, which can induce fatal fulminating hepatitis in severe cases. The HBV reactivation in lymphoma patients is related to multiple factors, such as age, sex, HBV infectious state, HBV genotypes and gene mutations, and antitumor drugs. It's necessary to strengthen monitoring, prevention and treatment to HBV reactivation in the process of dealing with lymphoma. This review focuses on the epidemiological characteristics of lymphoma and HBV, as well as the risk factors, morbidity, pathogenesis, clinical feature, suggestion on prevention and treatment of HBV reactivation.

Effect of Emodin Combined with AZT on the Proliferation and the Expression of BCL-2, NF-κB, TGF-β in the Leukemia Stem Cells-KG-1a cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Emodin combined with 3'-azido-3'-deoxythymidine (AZT) on the proliferation and apoptosis of concentrated leukemia stem cells (CLSC)-human acute myeloid leukemia KG-la cells and expression of BCL-2, NF-κB and TGF-β.</p><p><b>METHODS</b>The tumor stem cell-like subpopulation in human leukemia cell line KG-1a was enriched with 5-fluorouracil (5-FU). The CD34⁺ CD38⁻ subpopulation in the KG-1a cells was detected with flow cytometry, the cell proliferation was detected by MTT method to study the of Emodin and AZT in the CLSC. The cell apoptosis was analyzed by flow cytometry. The expression of NF-κB, BCL-2 and TGF-β mRNA and proteins were measured with RT-PCR and Western blot respectively.</p><p><b>RESULTS</b>As compared with cells treated with mentioned above drugs alone, the inhibition of proliferation potential and apoptosis rate of cells in combination group markedly increase with time and concentration dependent member (P < 0.01), the expression of NF-κB, BCL-2 and TGF-β mRNA and proteins decreased.</p><p><b>CONCLUSION</b>Emodin combined AZT can synergistically inhibit the proliferation, induce cell apoptosis, and down regulate the expression of NF-κB, BCL-2 and TGF-β mRNA and proteins in the CLSC, the possible mechanism of synergistic effect may be associated with inhibiton of BCL-2 activation and down-regulation of the expression of NF-κB, and TGF-β.</p>

Recent advances in therapy of follicular lymphoma / 中国实验血液学杂志

Follicular lymphoma is a common pathological subtypes of lymphoma, it ranked only second to diffuse large B-cell lymphoma, accounts for 22% of non Hodgkin's lymphoma. Follicular lymphoma is a displaying biologically and clinically diverse disease. Patients may present indolent, asymptomatic disease or more aggressive, symptomatic disease with high tumor burden. Decision-making to treat in the frontline is based on histology manifestation, tumor burden and patient symptoms. Treatment for follicular lymphoma includes radiotherapy, chemotherapy, immunological therapy and autologous stem cell transplantation or allogeneic stem cell transplantation.Radiation therapy is the first treatment of early stage follicular lymphoma. For advanced follicular lymphoma chemotherapy, chemotherapy combined immunotherapy or immune radiotherapy, stem cell transplantation may be chosen. In recent years, drugs for lymphoma including bortezomib, lenalidomide, Ofatumumab, Epratuzumab and so on, and the therapeutic scheme present more and more update. In this article the advances of treatment for follicular lymphoma are summarzied.

Effects of AZT on leukemia cell line KG-1a proliferation and telomerase activity / 中国实验血液学杂志

This study was purposed to investigate the effect of 3'-azido-2', 3'-dideoxythymidine (AZT)on the proliferation and telomerase activity of human acute myeloid leukemia cell line KG-1a. The effect of proliferation was detected by MTT assay after the KG-1a cell were stimulated for 24, 48 and 72 h with different concentrations of AZT; telomerase activity was detected with TRAP-PCR-ELISA assay; RT-PCR was used to detect telomerase hTERT mRNA expression. The results showed that the proliferation of KG-1a cells was inhibited in a time and concentration dependent manner after exposure to AZT for 24, 48 and 72 h; the KG-1a cells decreased in S phase and increased in G(2)/M phase with the increasing of the concentration of AZT; telomerase activity and hTERT-mRNA expression in the experimental groups decreased after treated with AZT, which was positively correlated with concentration of AZT. It is concluded that AZT inhibits KG-1a cell proliferation and induces apoptosis, which maybe related with its decreasing the telomerase activity and hTERT mRNA expression.

Relationship of MPO and NQO1 gene polymorphisms with susceptibility to acute leukemia / 中国实验血液学杂志

The aim of this study was to investigate the relationship of the gene polymorphisms of myeloperoxidase (MPO) and NAD (P) H: quinone oxidoreductase 1 (NQO1) with the susceptibility to acute leukemia (AL) in Chinese Gansu population. A 1:1 paired case-control study of 150 patients with acute leukemia and 150 cancer-free inpatients as a control was conducted to detect the polymorphisms of MPO and NQO1 by LDR techniques. The results showed that the MPO-463A genotype frequency in patient group was lower than that in control group, and there was significant difference of MPO (G-463A) genotype between patient group and control group (χ(2) = 11.828, P < 0.05, OR = 0.368, 95%CI = 0.205 - 0.610). The NQO1-609T genotype frequency in patient group was higher than that in control group, and there was significant difference of NQO1 (C-609T) genotype between patient group and control group (χ(2) = 17.931, P < 0.05, OR = 1.428, 95%CI = 1.237 - 3.339). The combined gene analysis showed that the AML risk in patients carrying the wild genotypes of MPO and NQO1 was dropped to 33.6%. It is concluded that the MPO and NQO1 gene polymorphisms are associated with susceptibility to AL. The AL risk may decrease in patients carrying MPO (G-463A) mutant gene (GA/AA), while the AL risk may increase in patients carrying NQO1 (C-609T) mutant gene (TC/TT). The combined effect of MPO and NQO1 wild genotypes may further decrease AL risk.

Clinical analysis of 8 cases of hepatitis-associated aplastic anemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the clinical characteristics of hepatitis-associated aplastic anemia (HAAA). A retrospective analysis was conducted among 8 cases of established HAAA in light of the clinical and laboratory findings and the patient outcomes.</p><p><b>METHODS</b>Serum samples from 8 patients with HAAA were tested for the antibodies to hepatitis viruses A, B, C, D, E and CMV, and 7 patients showed negative serological results while only one was positive for HBsAg. The percentage of CD4(+) cells was significantly lowered while the percentage of CD8(+) cells significantly increased to result in a lowered ratio of CD4(+)/CD8(+) cells in these HAAA patients. A shift in the Th1/Th2 and Tc1/Tc2 balance to a Th1 and Tc1 dominance was noted. The percentage of Treg cells was obviously decreased. Significant increments were found in the serum levels of interleukin-2, THF-α and interferon-γ. Three of the patients responded to immunosuppresssive treatment; one patient achieved a complete remission, two had a partial remission, and five failed to respond to the therapy and died.</p><p><b>CONCLUSIONS</b>HAAA may not have an obvious association with viral infections as by hepatitis virus A, B, C, D, or E, and its pathogenesis often involves abnormalities of the T cell immunity. Commonly with a poor prognosis, HAAA is associated with a high mortality rate.</p>

Relation of GSTP1 and CYP2E1 polymorphisms with susceptibility to acute leukemia / 中国实验血液学杂志

This study was aimed to investigate the relation of glutathione S-transferase pI (GSTP1) and cytochrome P450 enzyme 2E1 (CYP2E1) gene polymorphisms with the susceptibility to acute leukemia (AL) in Chinese population. The GSFP1 and CTP2E1 gene polymorphisms in 150 patients with AL and 150 patients with non-hematological diseases or non-tumor as controls were detected by means of case-control paired 1:1 method and ligase detection reaction (LDR) techniques. The results indicated that the frequently of G allele and Ile/Val + Val/Val of GSTP1 gene (26.7%and 44% respectively) in AL group were higher than those in control group (10% and 16% respectively); the AL risk for persons with Ile/Val + Val/Val was 3.260-fold (95%CI = 1.527 - 5.236) of persons with Ile/Ile. The further stratified analysis showed the frequency of Ile/Val + Val/Val in AML group was higher than that in control group (55% vs 16%, p < 0.05); the AML risk for persons with Ile/Val + Val/Val was 2.214-fold (95% CI = 1.009-3.260) as persons with Ile/Ile. The frequencies of C2 allele (16.7%) and C1C2/C2C2 of CYP2E1 gene (30%) in AL group seemed higher than those in control groups (13.9% and 26%), but the difference between them was not statistical significant (p > 0.05). The further stratified analysis showed that C1C2/C2C2 of CYP2E1 gene occurred more frequently in AML group (36%) than that in control group (32%), but there was no statistical difference between them (p > 0.05). Combined genotype analysis showed that the AML risk for persons in combination of lle/Val + Val/Val of GSTP1 gene with C1C2 + C2C2 of CYP2E1 gene increased by 3.208-fold. It is concluded that the GSTP1 gene is related with susceptibility to AML, the AL risk for persons with lle/Val + Val/Val of GSTP1 gene decreased, while CYP2E1 gene is not related with susceptibility to AL, the AML risk for persons in combination of GSTP1 wildtype with CYP2E1 hybrid and mutant genotype can be further decreased.

Apoptosis-inducing effect of clostridium difficile toxin A on K562 cells and its mechanism / 中国实验血液学杂志

This study was purposed to investigate the growth inhibition and apoptosis-inducing effect of Clostridium difficile toxin A (TcdA) on the leukemia cell line K562. The proliferative activity of K562 cells exposed to Tcd A was tested by MTT assay, cell apoptosis was detected by flow cytometry; immunocytochemistry and colorimetric assay were employed to detect the protein expressions of BCL-2/BAX and the activity of Caspase-3, respectively. The results indicated that the proliferation of K562 cells was inhibited in a time-and dose-dependent manner after exposure to Tcd A for 24, 48 and 72 hours, the cells displayed the typical apoptotic, morphological changes, the expression of BCL-2 protein was down-regulated but the expression of BAX protein was signficantly increased, compared with control group (p < 0.05). In addition, caspase-3 was activated in a concentration-dependent manner. It is concluded that Tcd A inhibits cell growth of K562 by inducing apoptosis, and the up-regulation of BAX protein and activation of caspase-3 may play important roles in these processes.

Effects of Clostridium difficile toxin a on proliferation of K562 cells / 中国实验血液学杂志

This study was aimed to investigate the effect of clostridium difficile toxin A (Tcd A) on proliferation of K562 cells and its mechanism. The proliferative activity of K562 cells exposed to Tcd A was tested by MTT assay; cell cycle distribution and mitochondrial membrane potential were analyzed by flow cytometry; the protein expression of cytochrome C and DNA fragmentation were observed by immunohistochemistry staining and agarose gel electrophoresis respectively. The results indicated that Tcd A inhibited proliferation of K562 cells in a time-and concentration-dependent manner. Cells were arrested at G(0)/G(1) phase. Peak of apoptosis appeared. The protein expression of cytochrome C increased as compared with control group (p < 0.05). Agarose gel electrophoresis of DNA from K562 treated with Tcd A revealed a "ladder" pattern. It is concluded that clostridium difficile toxin A can inhibit proliferation and induce apoptosis of K562 cells. The mechanism may be in relation to decrease of mitochondrial membrane potential and the release of cytochrome C from mitochondria matrix.