11例伴有t(7;11)(p15;p15)的急性髓系白血病患者的临床和实验室分析

目的 分析伴有t(7;11)(p15;p15)的急性髓系白血病(AML)患者的临床和实验室特征.方法 对11例伴有t(7;11)(p15;p15)的AML患者进行回顾性分析,包括细胞形态学、细胞免疫表型、细胞遗传学和临床预后.结果 11例患者中8例为女性,AML-M2a6例,M4、M5各2例,M61例.11例患者均表达CD33,其中10例表达CD117、CD13,7例表达HLA-DR,6例表达CD34.11例患者染色体核型均显示有t(7;11)(p15;p15),其中1例伴有+8.共9例患者检测FLT3-ITD、TKD突变,其中1例FLT3-ITD突变阳性.11例患者仅2例存活,1例失访;其余8例均死亡.结论 t(7;11)(p15;p15)异常是一种少见的染色体易位,伴有该异常的AML患者具有贫血、血小板减少、白细胞升高的临床特征,预后不良.

Abstract：

Objective To investigate clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with t(7;11)(p15;p15).Methods Eleven patients with t(7;11)(p15;p15) were retrospectively reviewed involved in cell morphology, immunophenotype, cytogenetics as well as clinical features and prognosis.Results Eight patients out of the eleven were female, six patients were AML-M2a, two M4,two M5, and one M6.All the 11 cases expressed CD33, 10 expressed CD117 and CD13, HLA-DR and CD34 was expressed in 7 and 6 patients, respectively.Karyotypes of all the patients were t ( 7; 11 ) ( p15; p15 ), additional trisomy 8 were found in only one patient.FLT3-ITD was positive in one of nine patients who were analysed for FLT3-ITD and FLT3-TKD.Two patients were alive, and one lost to followed up, while the rest of eight were dead.Conclusion The t(7;1 I )(p15;p15) abnormalities is one of rare chromosomal translocation in patients with AML.AML patients with t(7; 11 ) ( p15 ;p15 ) have clinical features of anemia, thrombocytopenia, higher white blood cell, and poor prognosis.     

16例伴19p13异常急性淋巴细胞白血病患者的临床和实验室研究

目的 分析伴19p13异常的急性淋巴细胞白血病(ALL)患者的临床和实验室特征:方法 对16例伴19p13异常的ALL患者的细胞形态学、免疫学、细胞遗传学和临床特点进行回顾性分析,并对t(1;19)组和der(19)组的临床和实验室资料进行对比分析.结果 伴19p13异常的ALL占同期ALL的4.02%,其中t(1;19)(q23;p13)15例[平衡易位t(1;19)(q23;p13)8例,不平衡易位der(19)t(1;19)(q23;p13)7例],t(17;19)(q22;p13)1例,t(1;19)组的外周血门细胞汁数和骨髓原始幼稚淋巴细胞比例明显高于der(19)组,而der(19)组的预后较t(1;19)组好.结论 19p13异常是ALL的一个非随机的染色体改变;伴有该异常的ALL患者具有独特的I临床特征和小良预后.     

Inv(16)急性髓系白血病的分子细胞遗传学研究

Inv(16 ) (p13q2 2 )或t(16 ;16 ) (p13q2 2 )是急性髓系白血病(AML)特征性染色体异常,通常见于AML M4EO亚型,占总AML患者的5 % [1] 。其分子特征为CBFB/MYH11融合基因形成。最新WHO分型中inv(16 ) /HY11 CBFB为一个独立类型[2 ] 。我们应用荧光原位杂交(FISH)技术对临床上诊断为M4EO及伴有嗜酸粒细胞增高的AML患者进行研究,回顾性分析inv(16 )患者临床与实验室特点。病例和方法1　病例　我院1998～2 0 0 2年有细胞遗传学资料的AML患者5 30例,选择伴有嗜酸粒细胞增高的AML患者32例(核型伴有2 2三体3例)作为研究对象,其中…     

伴有t(6;9)核型畸变的急性髓系白血病11例的特征分析

为了探讨伴有核型畸变t(6;9)(p23;q34)急性髓系白血病(AML)的特性,本研究对11例此类疾病患者的实验室及临床资料进行了回顾性分析,包括免疫表型分析和实时荧光定量PCR检测结果分析。结果显示,11例患者FAB分型以M2最多见,占6例,M4和M5各2例,MDS-RAEBT 1例;10例外周血白细胞数升高,骨髓病态造血2例,嗜碱细胞增多4例;细胞遗传学分析显示,6例伴有附加染色体异常;免疫表型检测表明,100%表达CD117、CD33、CD13、HLA-DR、CD38、CD123;基因分析显示,11例患者NPM1突变均为阴性,WT1基因表达水平普遍升高(7/7),7例中有3例具有FLT3-ITD。在住院治疗的7例患者中,1例未化疗即死亡,6例第1疗程接受标准剂量的DA或IA方案均无效,改用其他方案后3例无效死亡,3例获完全缓解,其中2例缓解后很快复发死亡。结论:伴有t(6;9)核型畸变的AML是一类独特的预后极差的白血病,经典的IA或DA方案化疗效果差,有效的治疗方案有待进一步研究。     

11q23异常儿童急性白血病的临床及实验室分析

目的　研究伴 11q2 3异常儿童急性白血病 (AL)的形态学、免疫学、细胞遗传学与其临床特征和预后的关系。方法　对 32 0例AL中 18例伴有 11q2 3异常的患儿进行回顾性分析 ,包括细胞形态学观察、流式细胞仪细胞免疫表型检测、R带核型分析和临床预后。以同期核型正常的 2 0例AL患儿作为对照。结果　 18例伴 11q2 3异常AL患儿中 14例为急性淋巴细胞白血病 (ALL) ,4例为急性髓系白血病 ,其中M5b3例 ,M2a1例。进行免疫表型分析的 16例患儿中 ,13例有淋系抗原表达 ,3例除表达髓系抗原外均显示CD34 阳性。异常核型有 6种 :t(4 ;11) (q2 1;q2 3) 6例 ;t(10 ;11) (p13;q2 3) 3例 ;t(11;19) (q2 3;p13) 1例 ;t(11;17) (q2 3;q11) 1例 ;t(8;11) (q2 3;q2 3) 1例 ;del(11) (q2 3) 6例。本组AL完全缓解 (CR)率为 72 .2 % ,与对照组的 80 .0 %相比 ,差异无显著性 (P >0 .0 5 ) ,而死亡率为 6 1.1% ,与对照组的 2 5 .0 %相比 ,差异有显著性 (P <0 .0 5 )。结论　 11q2 3异常主要见于儿童ALL和急性单核细胞白血病 ,具有较为独特的临床、血液学和预后特点。     

急性髓系白血病NPM1基因突变检测的临床意义

目的 探讨初诊急性髓细胞白血病(acute myeloid leukemia,AML)患者NPM1基因突变发生率及其与染色体核型和FAB亚型之间的关系,并分析NPM1基因的突变类型.方法 选取2004至2010年中日友好医院血液科99例初诊AML患者.采集患者骨髓标本,采用聚合酶链反应(polymerase chain reaction,PCR)扩增基因组DNA,并采用变性聚丙烯酰胺凝胶电泳(polyacrylamide gel electrophoresis,PAGE)和毛细管电泳两种方法对AML患者NPM1基因突变进行检测.应用G显带方法对其中72例初诊AML患者进行细胞遗传学分析,同时对10例NPM1突变阳性患者进行直接测序分析.NPM1插入突变在各亚型患者中发生率的比较采用x2检验.变性PAGE和毛细管电泳两种方法检测NPM1基因突变发生率的比较采用McNemar检验.结果 毛细管电泳法与变性PAGE法检测AML患者NPM1基因插入突变发生率分别为15％ (15/99)和11％ (11/99),差异无统计学意义(x2 =2.25,P＞0.05).NPM1插入突变在各亚型患者中发生率分别为:急性粒细胞白血病部分分化型(M2)(27％,8/30)、急性单核细胞白血病(M5)(32％,6/19)、红白血病(M6)(13％,1/8),差异无统计学意义(x2=1.06,P＞0.05),其余亚型未检测到NPM1插入突变.49例AML异常核型患者的NPM1插入突变发生率为4％ (2/49),23例正常核型患者的NPM1插入突变发生率为26％ (6/23),差异有统计学意义(x2=5.61,P＜0.05).10例NPM1基因插入突变均为A型突变(c.860_863 dupTCTG).突变导致NPM蛋白羧基末端读码框移,末尾7个氨基酸WQWRKSL被11个氨基酸CLAVEEVSLRK所代替.2例患者检测到内含子缺失突变,分别为IVS10-18_-15delCTTT和IVS10-17-15delTTT.结论 NPM1插入突变为AML患者常见基因改变,正常核型患者插入突变发生率高于异常核型患者.在NPM1基因内含子区发现2例缺失突变.     

176例急性髓性白血病患者的细胞遗传学及疗效分析

目的 :探讨急性髓性白血病 (AML)患者的细胞遗传学分型与疗效的关系。方法 :初诊的 176例AML患者进行形态学分型后 ,取骨髓行常规G显带或荧光原位杂交进行核型检测 ,并对核型与疗效关系进行分析。结果 :176例患者中 ,5 6 2 %的患者出现核型异常 ,其中t( 8;2 1) 16例 ,t( 15 ;17) 2 4例 ,inv( 16) 4例 ,11q2 3 (MLL) 2例 ,其他异常 5 3例。具有t( 8;2 1)、t( 15 ;17)或inv( 16)的患者的总体CR率 ( 80 % )显著高于其他患者 ( 62 % ) (P <0 0 0 1)。超过 60岁的患者 15例 ,其中 2例核型正常 ,13例属于其他异常 ,老年患者CR率 ( 2 7 3 % )远低于非老年患者( 69 7% ) (P <0 0 0 1)。结论 :5 6 2 %的AML患者可出现染色体异常 ,这些异常的核型可作为预后评估的指标 ,同时有助于AML的疗效判断及指导治疗     

1例罕见的t(15;17)急性早幼粒细胞白血病(M_3)复发时进展为急性原粒细胞白血病(M_1)

首次报道1例伴粒细胞生成异常的急性早幼粒细胞白血病(APL,M_3型)复发时进展为骨髓增生异常综合征(MDS),继而表现为t(7;21)急性原粒细胞白血病(AML,M_3型)。迄今尚无类似病例报道,该例亦是首次在AML病例中出现t(7;21)染色体异常的患者。     

伴t(16;21)(p11;q22)的恶性血液病的临床和实验分析

目的探讨伴t(16;21)(p11;q22)的恶性血液病的临床及实验室特征。方法骨髓细胞24 h培养后按常规方法制备染色体,用RHG显带技术进行细胞遗传学分析。结果 1例M2的患者其核型分析结果有t(16;21)(p11;q22)的异常,临床和血液学改变符合急性髓细胞白血病-M2a诊断,化疗后未获得完全缓解,中位生存期为6个月。结论 t(16;21)(p11;q22)是一类很独特的白血病亚型有关的易位,为少见的非随机的染色体易位,其临床预后差。     

21例伴t(11;19)(q23;p13)白血病的临床和实验室特征

目的探讨伴t(11;19)(q23;p13)白血病临床实验室特点。方法回顾性分析21例初诊t(11;19)(q23;p13)患者的临床实验室资料,包括核型分析、荧光原位杂交、融合基因、细胞免疫表型等。结果 21例患者中,16例为t(11;19)(q23;p13.1),核型表现为(11q+,19p–),伴有融合基因MLL-ELL阳性。男7例,女9例。分型诊断:1例AML-M2,3例AML-M4,10例AML-M5,另2例为CMML;5例为t(11;19)(q23;p13.3),核型表现为(11q–,19p+),伴有融合基因MLL-ENL阳性。1例男性,4例女性。分型诊断:3例proB-ALL,1例preB-ALL,1例T-ALL。结论 t(11;19)(q23;p13)为少见的非随机染色体易位,t(11;19)(q23;p13.1)主要在成人急性髓系白血病(AML)出现,且与单核系相关,而t(11;19)(q23;p13.3)主要在婴幼儿及儿童急性淋巴细胞白血病(ALL)中出现。     

Adipocytes: A Novel Target for IL-15/IL-15Rα Cancer Gene Therapy

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Exogenous pathogen and plant 15-lipoxygenase initiate endogenous lipoxin A4 biosynthesis

Lipoxin A4 (LXA4) is a potent endogenous lipoxygenase-derived eicosanoid with antiinflammatory and proresolving properties. Supraphysiological levels of LXA4 are generated during infection by Toxoplasma gondii, which in turn reduces interleukin (IL) 12 production by dendritic cells, thus dampening Th1-type cell-mediated immune responses and host immunopathology. In the present work, we sought evidence for the structural basis of T. gondii's ability to activate LXA4 biosynthesis. Proteomic analysis of T. gondii extract (soluble tachyzoite antigen [STAg]), which preserves the immunosuppressive and antiinflammatory activity of the parasite, yielded several peptide matches to known plant lipoxygenases. Hence, we incubated STAg itself with arachidonic acid and found using LC-UV-MS-MS-based lipidomics that STAg produced both 15-HETE and 5,15-diHETE, indicating that T. gondii carries 15-lipoxygenase activity. In addition, T. gondii tachyzoites (the rapidly multiplying and invasive stage of the parasite) generated LXA4 when provided with arachidonic acid. Local administration of a plant (soybean) lipoxygenase itself reduced neutrophilic infiltration in murine peritonitis, demonstrating that 15-lipoxygenase possesses antiinflammatory properties. Administration of plant 15-lipoxygenase generated endogenous LXA4 and mimicked the suppression of IL-12 production by splenic dendritic cells observed after T. gondii infection or STAg administration. Together, these results indicate that 15-lipoxygenase expressed by a pathogen as well as exogenously administered 15-lipoxygenase can interact with host biosynthetic circuits for endogenous "stop signals" that divert the host immune response and limit acute inflammation.     

Mesenteric and omental cysts: An ultrasonographic and clinical study of 15 patients

The clinical and ultrasonographic (US) features of 15 cases of mesenteric or omental cyst are herein described. This series included seven male and eight female patients, whose age ranged from 2–89 years. Correct clinical diagnosis was made in two children only, but preoperative US examination accurately demonstrated the lesion in 11 of 13 patients (85%). These cystic lesions usually had a thin wall, internal septations, and fluid content with sedimentation. Enteric duplication cysts had a relatively thick wall merging with the muscle layer of bowel loop, and multiloculation was noted mainly with cystic lymphangiomas or pseudocysts. The diagnostic and surgical management of these lesions are briefly reviewed and their US appearance is illustrated.     

Analytical and clinical performance of different platforms simultaneously detecting 15 antinuclear antibodies

BackgroundAntinuclear antibodies (ANAs) are invaluable biomarkers for the diagnosis of autoimmune diseases (AIDs). This study aims to compare the performances of line immunoassay (LIA), multiplex bead‐based flow fluorescent immunoassay (MBFFI), and magnetic bar code immunofluorescence assay (MBC‐IF) to detect ANA‐Profile‐15S.MethodsIn total, 184 samples from AID patients and 50 healthy controls (HCs) were collected. Fifteen ANAs (anti‐dsDNA, nucleosome, histone, Sm, PCNA, ribosomal‐P, SS‐A/Ro52, SS‐A/Ro60, SS‐B/La, centromere B [CENP‐B], Scl‐70, U1‐snRNP, AMA‐M2, Jo‐1, and Pm/Scl) were subjected to parallel detection by the LIA, MBFFI, and MBC‐IF. The consistency between assays was analyzed. The discrepant results were further examined by chemiluminescent immunoassay (CLIA).ResultsAnti‐SS‐A/Ro52 and SS‐A/Ro60 autoantibodies were the most common autoantibodies in ANA positive‐profiles, and were detected with equal efficiency by the LIA, MBFFI, and MBC‐IF (p = 0.101 and p = 0.732, respectively). The three assays showed excellent agreement (consistency range: 66.5%–97.5%), and total consistency was 85.8%. The MBFFI and MBC‐IF assays were in good agreement in terms of ANA‐Profile‐15S determination; the kappa coefficient ranged from 0.59 to 0.95, except for the PCNA and PM‐Scl. Of the 262 re‐assessed divergent results, 124 (47.33%) were positive on CLIA; the various autoantibodies exhibited variable patterns. More importantly, the ANA‐Profile‐15S results of the MBFFI and MBC‐IF accurately identified patients with AID; the area under the curves ranged from 0.642 to 0.919.ConclusionsThe novel MBFFI and MBC‐IF assay performed well in detecting ANA‐Profile‐15S. The application of MBFFI and MBC‐IF play important roles in laboratory diagnosis of AIDs.     

猪苓多糖联合白细胞介素15增强人外周血单个核细胞对K562细胞杀伤活性的影响

目的研究猪苓多糖联合白细胞介素（interleukin,IL）15对人外周血单个核细胞（peripheral blood mononuclear cells,PBMC）增殖的影响,探讨该效应细胞对人慢性髓细胞白血病K562细胞株增殖的抑制作用及可能的机制。方法密度梯度法分离PBMC,分别应用IL 2、IL 15、猪苓多糖、猪苓多糖+IL 2及猪苓多糖+IL 15刺激PBMC增殖,获得效应细胞,流式细胞仪（FCM）检测PBMC中T细胞、NK细胞活化的免疫表型;双抗体夹心酶联免疫吸附测定（ELISA）法检测效应细胞培养上清中干扰素γ（IFN γ）和肿瘤坏死因子α（TNF α）的水平;四甲基偶氮唑蓝（ MTT）比色法检测效应细胞对靶细胞的细胞毒作用。结果猪苓多糖联合IL 15能刺激PBMC中T细胞及NK细胞增殖,在促进NK细胞增殖作用上具有协同作用;能上调效应细胞培养上清中IFN γ和TNF α的水平,且具有协同作用;并能增强效应细胞对靶细胞的杀伤活性,大致呈时间 效应趋势。结论猪苓多糖+IL 15能够增强PBMC对K562细胞株的细胞毒作用,表现为肿瘤细胞增殖抑制率（IR）提高,杀伤机制可能与其刺激T细胞及NK细胞增殖,同时细胞培养上清中细胞因子IFN γ和TNF α的水平提高有关。     

Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis

The high affinity interleukin (IL)-15 receptor, IL-15Ralpha, is essential for supporting lymphoid homeostasis. To assess whether IL-15Ralpha's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Ralpha- and IL-2/15Rbeta-deficient mice. We find that IL-15Ralpha-competent, IL-2/15Rbeta-deficient cells are able to support IL-15Ralpha-deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Ralpha-mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Ralpha functions in vivo. Surprisingly, using IL-15- and IL-15Ralpha-deficient mixed chimera, we also find that IL-15 and IL-15Ralpha must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Ralpha is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Ralpha defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells.     

Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo

At least two types of interleukin (IL)-15 mRNA isoforms are generated by alternative splicing at the 5' upstream of exon 5 in mice. To elucidate the potential roles of IL-15 isoforms in immune responses in vivo, we constructed two groups of transgenic mice using originally described IL-15 cDNA with a normal exon 5 (normal IL-15 transgenic [Tg] mice) and IL-15 cDNA with an alternative exon 5 (alternative IL-15 Tg mice) under the control of an MHC class I promoter. Normal IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44(high) Ly6C(+)) of CD8(+) T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)-gamma production, but depletion of CD8(+) T cells exaggerated the bacterial growth, suggesting that the IL-15-dependent CD8(+) T cells with a memory phenotype may serve to protect against Salmonella infection in normal IL-15 Tg mice. On the other hand, a large amount of intracellular IL-15 protein was detected but hardly secreted extracellularly in alternative IL-15 Tg mice. Although most of the T cells developed normally in the alternative IL-15 Tg mice, they showed impaired IFN-gamma production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-gamma. Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo.     

伴两个t(15;17)易位的四倍体核型急性早幼粒细胞性白血病的实验和临床研究

目的 探讨伴有2个t(15;17)易位的四倍体核型APL的临床和实验室特点.方法 选取5例伴有2个t(15;17)易位为特征的四倍体核型APL病例,采用骨髓细胞直接法或短期培养法制备染色体,用R显带技术进行核型分析;采用流式细胞术对1例患者进行DNA倍性分析,检测APL患者白血病细胞表面CD2、CD13、CD15、CD33和CD34的表达;采用PML/RARα双色探针和FISH技术,检测其中1例APL患者的PML/RARα融合基因;采用RT-PCR技术,检测2例APL患者的PML/RARα融合基因的转录本.结果 5例APL患者均为男性,中位年龄38岁.骨髓细胞形态学检查显示,骨髓早幼粒细胞胞体巨大、胞核畸形.R显带染色体分析显示,5例APL患者均有以2个t(15;17)(q22;q12)为特征的四倍体或近四倍体核型细胞,其中1例同时伴有t(15;17)二倍体核型细胞和1个正常细胞,2例同时伴有正常核型的细胞.5例APL患者中,1例经间期FISH检测证实,含有2个PML/RARα融合荧光信号;2例经RT-PCR检测证实PML/RARα融合基因阳性.5例APL患者中,1例患者的白血病细胞仪表达CD33;其余4例表达CD13和CD33,其中2例同时表达CD2,1例同时表达CD34.采用流式细胞术对1例患者进行DNA倍体分析,发现四倍体克隆峰,其DNA指数为1.998,变异系数为8.2%.全部病例经全反式维甲酸和(或)砷剂治疗后均获得完全缓解.结论 伴2个t(15;17)易位的四倍体APL患者的骨髓涂片中均可见到巨大畸形白血病细胞;此类患者多为短型PML/RARα转录本;此类核型异常并不影响全反式维甲酸的疗效及预后.     

Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice

C57BL/6 mice genetically deficient in interleukin 15 (IL-15(-/-) mice) were generated by gene targeting. IL-15(-/-) mice displayed marked reductions in numbers of thymic and peripheral natural killer (NK) T cells, memory phenotype CD8(+) T cells, and distinct subpopulations of intestinal intraepithelial lymphocytes (IELs). The reduction but not absence of these populations in IL-15(-/-) mice likely reflects an important role for IL-15 for expansion and/or survival of these cells. IL-15(-/-) mice lacked NK cells, as assessed by both immunophenotyping and functional criteria, indicating an obligate role for IL-15 in the development and functional maturation of NK cells. Specific defects associated with IL-15 deficiency were reversed by in vivo administration of exogenous IL-15. Despite their immunological defects, IL-15(-/-) mice remained healthy when maintained under specific pathogen-free conditions. However, IL-15(-/-) mice are likely to have compromised host defense responses to various pathogens, as they were unable to mount a protective response to challenge with vaccinia virus. These data reveal critical roles for IL-15 in the development of specific lymphoid lineages. Moreover, the ability to rescue lymphoid defects in IL-15(-/-) mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine.