miR-103-3p regulates the differentiation of bone marrow mesenchymal stem cells in myelodysplastic syndrome

The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.

Severe inflammatory disorder in trisomy 8 without myelodysplastic syndrome and response to methylprednisolone:A case report

BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.

Flared inflammatory episode transforms advanced myelodysplastic syndrome into aplastic pancytopenia:A case report and literature review

BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia(AA),whereas advanced MDS is characterized by a phenotype of immune exhaustion.MDS can be normo/hyperplastic or hypoplastic.Generally,bone marrow cellularity and myeloblasts increase with disease progression.Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported.CASE SUMMARY A middle-aged Chinese woman had a 4-year history of leukocytopenia.Six months prior to admission,the patient developed gradually worsening fatigue and performance status.The leukocytopenia further progressed.She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears,an increased percentage of cluster of differentiation(CD)34+CD33+progenitors in immunotyping analysis,a normal karyotype in cytogenetic analysis,and the identification of somatic mutations in CBL,KMT2D and NF1 in molecular analysis.Initially,neutropenia was the predominant hematological abnormality,with mild anemia and thrombocytosis,and the degree of fatigue was far more severe than the degree of anemia.In the following months,the patient experienced several febrile episodes.Intravenous antibiotic treatments were able to control the febrile episodes,but the elevated inflammatory indices persisted.The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes.With recurrent flares of the inflammatory condition,agranulocytosis and severe anemia developed,with mild thrombocytopenia.During the patient’s hospitalization,computed tomography(CT)scans revealed the presence of extensive inflammatory lesions involving the lungs,mediastinum,pleura,gastrointestinal tract,peritoneum and urinary tract,with imaging features suggestive of the reactivation of disseminated tuberculosis.Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic,and the leukemic cells regressed,suggesting that both normal and leukemic hematopoiesis had been heavily suppressed.Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+cells and an immunological signature resembling that of severe AA(SAA),confirming the regression of the leukemic cells by autoimmune-mediated attacks.The patient demonstrated resistance to multiple drugs,including antituberculotics,recombinant human granulocyte colony-stimulating factor,broad-spectrum antibiotics,voriconazole,ganciclovir,immune suppressants,eltrombopag and intravenous immunoglobulin,which further worsened the hematological injury and patient’s performance status.The patient eventually died of overwhelming infection and multidrug resistance.CONCLUSION Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome:A case report and review of literature

BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.

MDS患者反复输注血小板的输血效果及其影响因素分析

目的:探讨骨髓增生异常综合征(MDS)患者反复输注血小板的输血效果,并分析影响血小板输注无效(PTR)的因素。方法:选取2019年1月—2022年12月潍坊市中医院收治的63例MDS患者为此次研究对象。依据PTR判定标准[输血后24 h校正血小板增高指数值(CCI)≤4、血小板回升率(PPR)≤20%]评估入组对象输血效果,logistic回归分析影响MDS患者PTR的因素。结果:入组63例MDS患者中,34例(53.97%)输注有效,29例(46.03%)输注无效。有效组与无效组在血小板抗体阳性、发热、脾肿大、P-选择素、人抗凝血酶3抗体水平比较上差异均有统计学意义(P<0.05),在性别、年龄、体重指数(BMI)、病程、WHO分型、国际预后评分(IPSS-R)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)比较,差异均无统计学意义(P>0.05)。单因素logistic分析结果显示,上述有统计学差异的指标均为影响MDS患者PTR的相关因素(P<0.05)。多因素logistic回归分析结果显示,血小板抗体阳性、P-选择素、人抗凝血酶3抗体升高均为影响MDS患者PTR的危险因素(OR=1.855、1.927、1.984,P<0.05)。结论:MDS患者反复输注血小板的输血效果不甚理想,PTR主要与血小板抗体阳性、P-选择素和人抗凝血酶3抗体水平有关。

伴RUNX1突变的MDS患者临床特征及预后分析

目的探究RUNX1突变在骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者中的临床特征及预后影响。方法收集2009年1月~2021年2月于上海交通大学医学院附属第六人民医院初诊的661例MDS患者的骨髓标本,采用二代测序检测一系列基因突变,重点回顾性分析RUNX1患者的临床特征、共同突变表达谱及预后意义。结果661例MDS患者中,65例伴有RUNX1突变。与无RUNX1突变患者比较,RUNX1突变患者骨髓原始细胞比例增加(P<0.001),其预后分层在修订国际预后积分系统(Revised International Scoring System,IPSS-R)较高危组和IPSS-M(IPSS-Molecular)高危/极高危组均占比较高(P<0.001)。59例RUNX1突变患者同时存在其他基因突变,突变频率较高的是ASXL1(24.62%)、TET2(24.62%)、EZH2(21.54%)和U2AF1(21.54%)等,主要为表观遗传学基因(63.62%)和剪切子基因(38.46%)。相关性分析发现,RUNX1突变与EZH2、PHF6和U2AF1突变呈正相关(Q<0.05)。RUNX1突变患者总体生存期较短(16个月vs 47个月,P<0.001),急性髓系白血病(acute myeloid leukemia,AML)转化风险较高(P<0.001),但在RUNX1主克隆和亚克隆突变间患者总体生存差异无统计学意义。结论RUNX1突变在MDS患者中发生率较高,且常伴有表观遗传学基因和剪切子基因突变。RUNX1突变预示着较短的总体生存期和较高的AML转化风险。

罗沙司他治疗难治性NSAA和低风险MDS相关贫血的疗效和安全性

目的探讨罗沙司他治疗难治性非重型再生障碍性贫血(NSAA)和低风险MDS(LR-MDS)的整组及亚组疗效、亚组疗效差异、疗效预测因素及安全性。方法收集2020年8月至2022年12月在北京协和医院血液内科就诊的难治性NSAA和LR-MDS患者,所有患者在罗沙司他治疗前,都接受过一线的标准治疗,并包括至少3个月以上的重组人促红细胞生成素(rhEPO)。患者均使用过罗沙司他2.5 mg/kg隔天1次,至少3个月,并随访至少8个月。分析患者临床特征、罗沙司他的疗效、疗效预测因素、不良反应、复发及疾病克隆演变情况。结果共纳入40例患者,包括24例难治性NSAA和16例LR-MDS。年龄18~81岁,中位年龄56岁,男性占40%。65%的患者有输血依赖。随访9~34个月,中位随访21个月,在第1、2、3、4、5、6个月及随访期末,分别有22.5%、25.0%、47.5%、55.0%、57.5%、60.0%和50.0%的患者达到血液学改善-红系反应(HI-E),未发现影响HI-E的因素。两组患者组间血红蛋白较基线变化在随访期末差异有统计学意义(P<0.05)。50%患者脱离输血依赖。22.5%患者报告了不良反应。28.5%患者在达到HI-E后复发,复发时间4~12个月,复发中位时间为7个月。在随访期末未观察到克隆演变。结论罗沙司他对传统疗法和rhEPO难治的NSAA或LR-MDS患者可能有效,不良反应轻微,复发率较低。难治性NSAA患者血红蛋白改善的程度可能更好。

单倍体供者与HLA相合供者HSCT治疗儿童MDS的疗效和安全性对比

目的评价单倍体供者移植作为替代方案用于异基因造血干细胞移植(allo-HSCT)治疗儿童骨髓增生异常综合征(MDS)的疗效及安全性。方法对2013年4月1日—2022年8月30日至苏州大学附属儿童医院接受allo-HSCT的22例儿童进展型MDS进行回顾性分析,其中全相合移植6例,单倍体移植16例。结果22例患儿均实现中性粒细胞植入,全相合组和单倍体组中性粒细胞植入中位时间分别为移植后11(10~12)天和11(9~17)天,血小板植入中位时间分别为移植后11(8~16)天和12(7~28)天。两组aGVHD的发生率分别为50%和100%(P=0.013),Ⅱ~Ⅳ度aGVHD发生率分别为0%和81%(P=0.001),aGVHD发生时间、Ⅲ~Ⅳ度aGVHD、cGVHD、广泛型cGVHD发生率无统计学意义。单倍体组移植后围植入综合征发生率为81%,显著高于全相合组的17%(P=0.011)。全相合组和单倍体组在CMV血症、EBV血症、出血性膀胱炎、肺部感染及神经系统并发症发生率上差异无统计学意义。至随访截止日期,全相合组中位随访时间为20.82(8.00~68.00)个月,单倍体组中位随访时间为21.38(2.77~69.77)个月,两组5年总体生存率分别为100%和(72.7±17.7)%,两组差异无统计学意义。结论单倍体移植与同胞全相合移植后细胞植入、严重的移植相关并发症发生率、免疫重建及长期存活率无明显差异,因此,对于无全相合供者的儿童MDS患者,单倍体供体移植可作为合适的替代方案。

BCOR突变通过PI3K/Akt/mTOR通路介导MDS细胞生物学行为改变的机制研究

目的 探讨BCOR(BCL6 co-repressor)基因突变介导骨髓增生异常综合征(myelodysplastic syndromes, MDS)细胞生物学行为的分子机制。方法 通过构建BCORP483L过表达慢病毒以及空载体病毒,转染K562细胞,采用集落形成实验检测BCOR突变对细胞克隆形成能力的影响,流式细胞术检测细胞凋亡、细胞周期,Western blot法和实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction, RT-qPCR)方法检测细胞焦亡和PI3K/Akt/mTOR通路分子水平,采用转录组测序技术(RNA-sequencing, RNA-Seq)检测分析BCORP483L突变对下游靶基因表达的影响。结果 BCORP483L突变显著地抑制细胞克隆形成能力,促进细胞凋亡,并导致细胞周期阻滞和细胞焦亡水平增加。RNA-Seq分析发现,BCORP483L突变后K562内与细胞凋亡、G2M周期检查点、慢性髓系白血病、细胞衰老、细胞内炎性反应相关的基因以及原癌基因MYC目标基因表达上调。Western blot法实验进一步证实,BCORP483L突变细胞的PI3K/Akt/mTOR通路明显受到抑制。结论 BCOR突变导致细胞PI3K/Akt/mTOR通路受到抑制,进而导致细胞凋亡增加、增殖受抑。BCOR突变能通过上调细胞衰老相关基因以及原癌基因MYC目标基因表达,提高细胞内炎性反应水平,从而促进MDS疾病进展。

PD-1/PD-L1在MDS原始细胞、T细胞亚群和Treg细胞中的表达及意义

目的:探讨PD-1/PD-L1在MDS原始细胞、T细胞亚群和Treg细胞中的表达及其意义。方法:以88例MDS患者和19例AML患者为研究对象,以缺铁性贫血和健康骨髓捐献者为对照。采用流式细胞术分别检测其MDS/AML原始细胞、T细胞亚群和Treg细胞中PD-1/PD-L1的表达,同时检测外周血清Th1/Th2/Th17相关细胞因子的表达水平。结果:低危MDS组原始细胞、T细胞亚群、Treg细胞中PD-1/PD-L1的表达水平均明显低于对照组、中高危MDS组和AML组(均P<0.01);细胞因子以Th1/Th17类型占优势。中高危MDS组和AML组原始细胞、T细胞亚群、Treg细胞中的PD-1/PD-L1表达均明显高于对照组和低危MDS组(均P<0.01);细胞因子以Th2类型和Treg类型(IL-10、TGF-β)占优势。治疗后,MDS缓解组原始细胞、T细胞亚群、Treg细胞中PD-1/PD-L1的表达较对照组均无明显差异(P>0.05)。MDS未缓解组原始细胞、T细胞亚群、Treg细胞中PD-1/PD-L1的表达均显著高于MDS缓解组和对照组(P<0.01)。结论:PD-1/PD-L1在MDS患者中存在高表达,Treg(IL-10、TGF-β)和Th2相关细胞因子占优势以及效应T细胞被抑制的微环境,有利于肿瘤细胞增殖和免疫逃逸,可能促进了MDS疾病的进展。

网织红细胞、血清铁蛋白、VitB_(12)联合检测在MDS与MA鉴别诊断中的应用价值

目的:探讨网织红细胞、血清铁蛋白(SF)、维生素B_(12)(VitB_(12))联合检测在骨髓增生异常综合征(MDS)与巨幼细胞贫血(MA)鉴别诊断中的应用价值。方法:选取2020年7月—2023年11月吉安市中心人民医院收治的MDS患者43例纳入MDS组,MA患者43例纳入MA组,另选取于本院体检的健康体检者43例纳入对照组,比较三组血浆网织红细胞、SF及血清VitB_(12)水平,通过受试者操作特征(ROC)曲线分析三项指标单独或联合检测对MDS的诊断效能。结果:MDS组、MA组网织红细胞血红蛋白(Ret-He)、未成熟网织红细胞指数(IRF)、中荧光强度网织红细胞比率(MFR)、高荧光强度网织红细胞比率(HFR)水平均高于对照组,差异均有统计学意义(P<0.05);MDS组、MA组的低荧光强度网织红细胞比率(LFR)均低于对照组(P<0.05);两组IRF、LFR、MFR、HFR水平比较,差异均无统计学意义(P>0.05);MDS组Ret-He水平低于MA组,差异有统计学意义(P<0.05);MDS组、MA组SF水平均高于对照组,差异均有统计学意义(P<0.05);MDS组血清VitB_(12)水平高于对照组,MA组血清VitB_(12)水平低于对照组,差异均有统计学意义(P<0.05);MDS组SF、VitB_(12)水平均高于MA组,差异均有统计学意义(P<0.05)。网织红细胞参数Ret-He与SF、VitB_(12)联合检测诊断MDS时ROC曲线下面积为0.942,高于三项指标单独检测曲线下面积0.755、0.813、0.830,差异均有统计学意义(P<0.05)。结论:网织红细胞联合SF和VitB_(12)对于指导MDS诊断具有一定的价值,MDS的SF、VitB_(12)均高于MA,Ret-He低于MA,可作为临床疾病鉴别的重要参考指标。

外周血涂片+骨髓涂片+流式细胞术联合应用对MDS早期诊断准确性的影响

目的 探讨在骨髓增生异常综合征(MDS)应用外周涂片联合骨髓涂片与流式细胞术进行早期诊断的临床效果。方法 选取2019年6月—2022年6月本院接收诊治的骨髓增生异常综合征患者120例作为此次研究对象,按照检验方式的不同将患者分为实验组和对照组,每组60例。其中,对照组单独使用外周血涂片进行MDS的早期诊断,实验组则联合外周血涂片、骨髓涂片和流式细胞术进行MDS的早期诊断。对比两组患者的诊断结果。结果 经过检查后,实验组患者的检测结果明显优于对照组,差异有统计学意义(P<0.05)。结论 将外周血涂片、骨髓涂片和流式细胞术联合起来进行MDS的早期诊断,检测准确性更高,能够为临床治疗提供更精准的数据支持。

Clinical management of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes

The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia

AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients (60.1% male,mean age 61.3 years,13% MDS,87% AML) had 594 unique hospitalizations during the study period.Thirtyfour patients (15.2%) were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001),prior diagnosis of CDI (P < 0.0001),receipt of cytarabine-based chemotherapy (P = 0.015),total days of neutropenia (P = 0.014),and total days of hospitalization (P = 0.005).Gender (P = 0.10),age (P = 0.77),proton-pump inhibitor use (P = 0.73),receipt of antibiotics (P = 0.66),and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.

Identification of SNP-containing regulatory motifs in the myelodysplastic syndromes model using SNP arrays and gene expression arrays

Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.

Large-vessel thrombosis in intestinal Behet's disease complicated with myelodysplastic syndrome and trisomy 8

Behet's disease is characterized by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis. Several studies have identified a relationship between MDS and Behet's disease, especially intestinal Behet's disease. Trisomy 8 seems to play an important role in these disorders as well. The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever. We also noted folliculitis on her upper back. Five days later, she began to experience diarrhea and abdominal pain. Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers. Later, she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection. The patient's clinical presentations met the criteria for Behet's disease. Six months after the bowel perforation event, we noted the development of pancytopenia in a routine laboratory examination. All the examinations led to the diagnosis of MDS with trisomy 8. The most unusual finding was that multiple large vessel thrombi developed during follow-up. Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Behet's disease. Moreover, the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8. Trisomy 8 must play a role in thrombosis. Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.

TET2 Expression in Bone Marrow Mononuclear Cells of Patients with Myelodysplastic Syndromes and Its Clinical Significances

Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells （BMMNC） of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [（0.41±0.28）% vs. （1.07±0.56）%] （P〈0.001）. Compared with lower expression group （TET2〈0.4） [（6.53±6.17）%], patients with higher expression of TET2 ≥0.4） presented significantly lower proportion of bone marrow blasts [（1.21±1.56）%1 （P〈0.05）. The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden （t=--0.398, P〈0.05） and IPSS r=-0.412, P〈0.05）. The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased, which might be useful as an important parameter for the evaluation of MDS clone burden.

Early Detection of Myelodysplastic Syndrome/Leukemia-associated Mutations Using NGS Is Critical in Treating Aplastic Anemia

Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases.However,due to recent advances in DNA sequencing technology,both spectnim and frequency of mutations can be accurately determined and monitored by next-generation sequencing(NGS)at initial diagnosis and during immunosuppressive therapy(1ST)in patients with AA or hMDS.This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper,precise,and on-time information to guide disease management,which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.

Novel spontaneous myelodysplastic syndrome mouse model

Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Platelet Doubling After First Decitabine Cycle Predicts Response and Survival of Myelodysplastic Syndrome Patients

Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice,and determine the predictive factors of response and overall survival(OS)in MDS patients.