Objective:To investigate the clinical effect of second-generation tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia ( CML) . Methods:A total of 64 patients with CML treated between January 2013 and December 2016 were selected as study subjects and treated with second-generation tyrosinekinase inhibitor ( TKI) . Among them,there were 41 cases treated with Nilotinib and 23 cases with Dasatinib. In patients treated by TKI,there were 13 cases receiving first-line medication and 51 cases receiving second-line medication. All were followed up for 6 ~ 54 months,median 18 months. The overall complete hematologic remission ( CHR) rate,CCyR rate,rate of major cytogenetic response ( MCyR),MMR rate,follow-up over-all survival rate ( OS) and event free survival rate ( EFS) were observed;Meanwhile,the responses of first-line and second-line treatment and adverse drug reactions were compared. Results:At the end of follow-up,43 cases continued second-generation TKI treatment, 14 cases died, 2 cases stopped medication, 2 cases were lost to follow up and 3 cases changed the medication regimen;In terms of overall responses to treatment,the rates of CHR, MCyR, CCyR and MMR were 98. 44%, 64. 00%, 59. 37% and 43. 75% respectively; In terms of overall survival status,OS and EFS decreased with duration of the disease. The rates of CCyR,MCyR and MMR of first-line treatment were significantly higher than the second-line treatment ( P < 0.05);There were no significant differences in the incidence of adverse drug reactions between Nilotinib and Dasatinib ( P >0.05) . Conclusion:The effect of Nilotinib and Dasatinib second-generation TKI in the treatment of CML is clear. The prognosis is good and safety is better; The effect of second generation TKI first-line treatment is better than second-line treatment in treating CML.

Objective To explore decitabine combined with small dose of homoharringtonine plus cytarabine and recombinant human granulocyte colony-stimulating factor (HAG) in patients with acute myeloid leukemia to provide new ideas and new directions for clinical treatment of acute myeloid leukemia.Methods Sixty-eight patients with acute myeloid leukemia treated at Wuxi Municipal People's Hospital were selected from January 2016 to October 2016.Using a random number table,patients were randomly divided into an observation group and a control group with 34 patients in each group.The observation group was treated with decitabine combined with small dose of HAG and the control group received cytarabine plus aclamycin and granulocyte colony-stimulating factor (CAG).Treatment efficacy,and levels of CD4 +,CD8 + and CD4 +/CD8 + as well as adverse reactions were compared between the two groups.Results The overall efficacy rate was 91.2％ which was higher than 67.6％ of the control group (P ＜ 0.05).There was no significant difference in the levels of CD4 +,CD8 + and CD4 +/CD8 + between the two groups before the treatment (P ＞ 0.05).After the treatment,levels of CD4 + and CD4 +/CD8 + were significantly higher in the observation group than in the control group and CD8 + was significantly lower in the observation group than in the control group (P ＜ 0.05).Adverse reactions included gastrointestinal reactions,dysfunction of liver,respiratory infection and fever,which relieved after management of antiemesis,and liver conserving,stomach conserving therapy,albumin infusion and support treatment.There was no significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion The capecitabine combined with low-dose HAG is effective and safe in patients with acute myeloid leukemia and is worthy of clinical promotion.

In this study, we investigated the anti-tumor activity both in vitro and in vivo of a polysaccharide obtained from Ganoderma lucidum on HL-60 acute myeloid leukemia cells, and focused on its targeting effect on mitogen-activated protein kinase (MAPK) pathways. It was found by the methods such as western blot and flow cytometry (FCM), that G. lucidum polysaccharide (GLP) blocked the extracellular signal-regulated kinase/MAPK signaling pathway, simultaneously activated p38 and JNK MAPK pathways, and therefore regulated their downstream genes and proteins, including p53, c-myc, c-fos, c-jun, Bcl-2, Bax, cleaved caspase-3 and cyclin D1. As a result, cycle arrest and apoptosis of HL-60 cells were induced. Therefore, GLP exerted anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.

目的 探讨诱导疗法对急性髓系白血病患者临床疗效及生活质量的影响.方法 选取2012年1月至2015年12月间在无锡市人民医院进行治疗的80例急性髓系白血病患者,回顾性分析患者采用标准剂量伊达比星联合阿糖胞苷诱导治疗的不良反应、疗效及复发情况.结果 标准剂量伊达比星联合阿糖胞苷方案诱导治疗对造血系统的毒性为92.5％,对感染、脱发、胃肠道反应也有一定毒性影响.80例患者中,预后良好24例,预后中等50例,预后不良6例.预后良好患者在第1个疗程完全缓解率为54.2％,好于预后中等患者和预后不良患者,预后良好患者在各个疗程2年生存(0S)率以及2年无复发生存期(DFS)均明显高于预后中等患者.结论 伊达比星联合阿糖胞苷诱导方案治疗急性髓系白血病患者生存状况明显优于常规治疗,有利于提高患者DFS和OS率,值得推广应用.

Two genome-wide association studies (GWASs) have identified several new acute leukemia susceptibility loci in populations of European descent. However, the roles of these loci in the development of acute leukemia in other populations are largely unknown.

Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. Methods and Results: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS) analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO) analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-κB pathway. Conclusions: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-κB signaling pathway in HH4 cells.

急性粒单核细胞白血病易发生牙龈、皮肤或中枢神经系统的髓外侵犯，本例患者诱导缓解期出现中枢浸润，符合CNSL只有少数在白血病的初期或首诊发生，大部分在缓解期发生的发病特点。在其中枢复发后采用中剂量Ara-C为主的诱导方案，联合IDA，MTX，VM-26和氟达拉滨，兼顾了中枢和外周系统的化疗。患者在达到完全缓解后序贯中剂量Ara-C和易透过血脑屏障的化疗药物使患者达到持续完全缓解而长期存活，为不能进行造血干细胞移植的患者提供了一种选择途经。

OBJECTIVE:To investigate the relationship between RAD51-G135C and XRCC3-C241T single nucleotide polymorphisms and onset of acute myeloid leukemia (AML).METHODS:The study was performed in 2 groups: AML patient group and normal person group as control group. Genomic DNA was extracted from peripheral blood cells of 545 AML patients and 1 034 normal persons. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by TaqMan probe technology and the ralatienship between RAD51-G135C/XRCC3-C241T polymorphisms and onset of acute myeloid leukemia was investigated.RESULTS:Compared with the control group, RAD51-G135C homozygous mutant (CC) could significantly increase the risk of AML patients (OR=3.07), and there was no statistical relationship between heterozygous mutant (GC) of RAD51-G135C and onset of AML. There was no statistical relationship between homozygous mutant (TT) of XRCC3-C241T and onset of AML, and the XRCC3-C241T heterozygous mutation type (CT) increased the risk of AML patients (OR=0.66).CONCLUSION:RAD51-G135C homozygous mutant and XRCC3-C241T heterozygous mutation significantly increase the risk of the AML onset, which can provide more predictive value for incidence of AML.

T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19(+) cell expression and decreased CD4(+)/CD8(+) cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19(+) cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4(+)/CD8(+) cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8(+) cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8(+) cells or lower levels of CD4(+)/CD8(+) cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult.

OBJECTIVE:The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the serum of patients with chronic myeloid leukemia (CML) and the effect of VEGF on cell proliferation.PATIENTS AND METHODS:Serum VEGF levels in 12 CML patients (7 chronic phase, 5 blast crisis phase) were measured using enzyme linked immunosorbent assay (ELISA). VEGF expression was interfered by transfection of K562 cells. VEGF mRNA levels in transfected K562 cells were determined using RT-PCR and the effect of VEGF on the proliferation of transfected K562 cells was investigated.RESULTS:VEGF expression levels were significantly higher in CML patients than normal controls and significantly increased during blast crisis phase than during chronic phase. Compared to controls, the proliferation of the K562 cells was suppressed when VEGF expression was inhibited. However, the inhibited proliferation of K562 cells after gene silencing of VEGF was partially abolished after introducing exogenous VEGF into the cells.CONCLUSIONS:VEGF plays an important role in the initiation and development of CML and monitoring serum VEGF assists guiding the treatment and predicting the prognosis of CML.

目的:探究急性白血病患者给予沙利度胺配合化疗在抗血管生长方面的临床成效.方法:选取我院2009年3月-2014年1月收治的86例急性白血病患者,随机分为研究组和对照组,每组43例.对照组患者给予常规化疗方案,研究组在对照组基础上给予沙利度胺配合化疗.观察两组患者治疗前后血浆VEGF,VEGFR,bFGF及MVD的水平变化.比较两组患者的临床疗效及不良反应发生率.结果:治疗前,两组患者VEGF、VEGFR、bFGF及MVD水平无显著差异(P＞0.05);治疗后,研究组患者VEGF、VEGFR、bFGF及MVD水平均低于对照组,差异有统计学意义(P＜0.05).研究组患者治疗的有效率为88.4％,对照组为76.7％,研究组显著优于对照组,差异具有统计学意义(P＜0.05).研究组不良反应发生率为79.1％,对照组为81.4％,差异无统计学意义(P＞0.05).结论:沙利度胺配合化疗治疗急性白血病能调控促血管生长因子水平,提高疗效,不良反应可耐受.

OBJECTIVE To evaluate the impact of Fc gamma receptor IIIa (FcγR IIIa) polymorphisms on the efficacy of rituximab (RTX) combined chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). METHODS FcγRIIIa polymorphisms were analyzed by PCR in 122 patients and 100 healthy controls. All patients received 8(4-12) cycles of RTX combined chemotherapy. RESULTS 78(63.93%) patients with F/F, 5(4.10%) with V/V, and 39(31.97%) with V/F were identified, which were not different compared to controls. Patients with different FcγRIIIa genotypes did not have any difference in terms of gender, age, molecular subtypes, lactate dehydrogenase (LDH) or international prognostic index (IPI). The overall response rate (ORR) was 89.35% with a complete response (CR) of 80.33% and a partial response (PR) of 9.02%. The ORR was 83.33%, 100.00% and 100.00% in F/F, V/V and V/F, respectively. A higher response rate was observed in V/V and V/F as compared with F/F (P<0.05). With a median follow-up of 35 months (range: 12-62 months), 46(37.71%) patients had relapsed and 40 (32.79%) cases progressed and ended in death. The 3-year progress-free survival (PFS) rate was 41.03%, 100.00%, 100.00% in F/F, V/V and V/F, respectively. The 3-year overall survival (OS) rate was 48.72%, 100.00% and 100.00% in patients with three genotypes. The PFS and OS rate were significantly higher in V/V and V/F as compared with F/F (P<0.05). CONCLUSION FcγR III a polymorphisms could predict response and prognosis of RTX combined chemotherapy for patients with DLBCL.

ObjectiveTo investigate the influence of the combination therapy VTD on coagulation in patients with refractory/relapsed multiple myeloma.MethodsWe obtained blood samples before start of treatment,and 1h after the first(day 1) and second(day 4) dose of bortezomib therapy,then mesured the prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin times(TT),anti-thrombin III activities(AT-Ⅲ),fibrinogen(FIB)and the maximum platelet aggregation rate in 3 hours,respectively.ResultsBefore start of treatment,and 1h after the fisrt and second dose of bortezomib therapy,it was found that APTT、PT、TT of the 28 patients were not statistically changed,while AT-Ⅲ and FIB were increased regardless of the p Values>0.05.However,the platelet maximal aggregation rate was actually decreased in the T0、 T1、T2,respectively.Only one person suffered from venous thrombosis(VET).ConclusionWhen patients with refractory/relapsed multiple myeloma treated with VTD,the coagulation had no significant change,but platelet aggregation was significantly decreased in a dose-and time-dependent manner.

The interleukin-23 (IL-23) and its receptor (IL-23R) mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C) have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML) patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.01-1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01-1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.

This study was aimed to investigate the correlation of FcγR polymorphisms with the susceptibility, severity and efficacy of immunotherapy for patients with immune thrombocytopenia (ITP). PCR and DNA sequencing were used to determine the polymorphisms of FcγRIIA, FcγRIIIA and FcγRIIB in 44 ITP patients, and in 97 healthy control subjects. The results indicated that FcγRIIIA-158V/F polymorphisms between patients and controls were statistically significantly different (P = 0.015); among FcγRIIIA genotypes, the frequency of 158V/V homotype was higher in ITP (P = 0.005). However, the FcγRIIA-131H/R or FcγRIIB-232T/I polymorphisms were not significantly different between patients and controls; there were no correlation of FcγRIIA, FcγRIIIA and FcγRIIB genotype frequencies with the platelet counts or the courses of ITP; among the 38 ITP patients who received treatments, the complete response (CR) rate was 42% (16/38), and partial response (PR) rate was 34% (13/38). The therapeutic response was significantly different between FcγRIIIA-158V/V homotype and 158F/V heterotype (P = 0.034). The CR of patients with 158V/V homotype was obviously lower than that of patients with 158F/V, but the frequencies of FcγRIIA and FcγRIIB genotypes not correlated with the responsiveness to treatment. The CR rate of 6 patients treated with rituximab was 67%, and PR rate was 17%. The overall response rate was as high as 84%, the adverse reactions were not observed. It is concluded that the polymorphism of FcγRIIIA-158V/F, but not FcγRIIA-131H/R or FcγRIIB-232T/I, correlates with the patient susceptibility and therapeutic response of ITP.

Childhood acute lymphoblastic leukemia (C-ALL) is the most common pediatric cancer. Although its etiology remains poorly understood, the hypothesis of ALL correlated with a genetic basis was examined through association studies based on candidate genes. Recently, two independent large-scale genome-wide association studies reported that the five single nucleotide polymorphisms (rs7073837; rs10821936; rs10994982; rs7089424; rs10740055) in the gene AT rich interactive domain 5B (ARID5B) at 10q21.2, were associated with the high incidence risk of C-ALL, especially with hyperdiploid lymphoblastic leukemia. Variations in these single nucleotide polymorphisms influence the risk of specific disease subtypes, and also possess race- and sex-differences in leukemia incidence. Further elucidation of the mechanisms through which ARID5B variants are involved in C-ALL not only has a great diagnostic value, but also a guidance for the clinical therapy, ultimately improving the prognosis of disease. Therefore, the related studies of ARID5B with C-ALL were summarized briefly in this review.

OBJECTIVE:JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF).METHODS:We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF.RESULTS:Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls.CONCLUSION:MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

The C3435T (Ile1142Ile) polymorphism of the multidrug resistance gene (MDR1) has been implicated in leukemia risk, but the reported results are inconsistent. Here we performed a meta-analysis to evaluate the association between C3435T polymorphism and the risk of leukemia using all case-control studies published before June 2011 according to PubMed. A total of 10 case-control studies were included in this analysis. We found that variant genotypes of C3435T (CT/TT) were significantly associated with an increased risk of leukemia (CT/TT vs. CC: odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.11-1.50, p = 0.284 for heterogeneity test). Additionally, the association was more significant in chronic leukemia (specifically B-cell chronic lymphocytic leukemia [B-CLL]) (OR = 1.94; 95% CI = 1.32-2.85, p = 0.648 for heterogeneity test) than in acute leukemia (OR = 1.19; 95% CI = 1.01-1.40, p = 0.616 for heterogeneity test), p = 0.021 for heterogeneity test between groups. These findings provide further evidence that the MDR1 C3435T variant may modify the susceptibility to leukemia.

Objective:To investigate the efficacy and toxicity of amifostine(AMF) combined with thalidomide on patients with myelodysplastic syndrome(MDS).Methods:23 MDS patients were treated with AMF and thalidomide.Results:The overall response rate was 60.9%,including complete response (CR) in 10(43.5%),partial response(PR) in 4(17.4%),No response(NR) was 9 cases(39.1%).7 cases attained hematological obvious improvement in leukocytes and 4 cases attained hematological improvement in platelets.The main side reaction was usually discomfort of digestive system,but all patients can endure.Conclusions:Aamifostine plus thalidomide may have a good therapeutic effects for MDS patients,and its clinical curative still needs further evaluation.

<正>患者,男,44岁,既往体健。2009年2月因"面白、乏力、皮肤出血点伴咳嗽1个月"至我院就诊。门诊查血常规三系降低,考虑全血细胞减少待查收入院。体检:贫血貌,皮肤散在淤点,浅表淋巴结未及肿大,胸骨无压痛,心肺无异常,腹平软,无压痛、反跳痛,肝脾肋下未触及。辅助检查:胸片、腹部B