AML／TMDS与MDS—AML的对比研究

目的：分析三系病态造血的急性髓系白血病(AML／TMDS)与骨髓增生异常综合征演变为急性髓系白血病(MDS—AML)的差异。方法：采用常规形态学和细胞化学染色方法观察患者外周血和骨髓细胞。结果：AML/TMDS患者血小板计数和外周原始细胞百分率高于MDS—AML(P＜0．05，P＜0．01)；小巨核细胞和Pseudo-pelger异常明显低于MDS-AML(P＜0．05，P＜0．01)，2组病例MPO染色阳性率基本一致，但AML/TMDS患者MPO积分显著高于MDS—AML(P＜0．01)。AML/TMDS患者多核原始红细胞明显低于MDS—AML(P＜0．05)；AML／TMDS与MDS—AML患者巨大血小板分别为23．1％和86．7％。结论：AML/TMDS与MDS—AML白血病克隆不同，正确诊断对确定方案、判断疗效及预后有重要意义。     

骨髓增生异常综合征相关性急性淋巴细胞性白血病(附7例报告)

目的 :探讨骨髓增生异常综合征相关性急性淋巴细胞白血病 ( MDS/ AL L)的特点。方法 :MDS/AL L与骨髓增生异常综合征相关性急性髓细胞性白血病 ( MDS/ AML )的临床及实验室特点进行比较 ,采用 t检验、检验统计。结果 :MDS转化成 AL L 8.14 % ,其类型为 型 5例 , 型 2例。 AL L类型 L1 1例 ,L2 6例。临床及血象在 MDS/ AML与 MDS/ AL L二组之间无明显差异。骨髓象二组之间差异较大。 MDS/ AL L在 MDS期部分类似一过性再生障碍性贫血 ,骨髓幼稚细胞均值为 0 .74 6,高于 MDS/ AML,( P<0 .0 1)。红系为 0 .0 8,低于 MDS/AML( P<0 .0 1)。巨核细胞低于 MDS/ AL L,但无明显差异。MDS/ AL L 在 MDS期及 AL L 期均罕见形态学改变。结论 :MDS/ AL L与 MDS/ AML有异质性。这与干细胞受累的水平不同有关 ,MDS/ AL L可能是在多能造血干细胞时受累     

急性髓系白血病伴三系病态造血(AML/TMDS)的观察及临床意义

目的 探讨急性髓系白血病伴三系病态造血(AML／TMDS)的生物学特征及I临床意义。方法 对225例急性髓系白血病(AML)进行骨髓细胞形态学观察，部分结合染色体检查及临床资料进行综合分析。结果 225例AML中30例伴有三系病态造血(TMDS)，占13．3％。除M2以外的AML，以M6和M4较高；染色体异常改变的比例高。AML／TMDs( )比AML／TMDS(-)组CR率低，CR持续时间短。结论 AML/TMDS可能是一种有特殊生物学特性的AML新亚型，临床疗效差，预后不良。     

原发性眼眶髓系肉瘤1例

髓系肉瘤(myeloid sarcoma,MS)又称粒细胞肉瘤(granulocytic sarcoma,GS),是原始或幼稚细胞的髓系细胞在髓外形成的实体肿瘤,可与急性髓系白血病(acute myeloid leukemia,AML)或骨髓异常增生综合征/骨髓增殖性疾病(myelodyplastic syndrome,MDS / myelodyplastic syndrome,MPN)同时发生,MS在AML中占2.5%~9.1%^[1]。     

细胞发育异常在骨髓增生异常综合征患者预后评估中的价值

目的:探讨骨髓细胞病态造血在骨髓增生异常综合征(MDS)向急性白血病转化及预后评估中的价值。方法:回顾性分析82例MDS患者骨髓细胞形态学、细胞遗传学及流式细胞术等相关资料,分析患者骨髓细胞病态造血特点及患者预后转归。结果:82例MDS患者中,25例转化为急性髓系白血病(AML),其中45例存在原始细胞增多中20例转化为急性白血病,37例无原始细胞增多中5例转化为急性白血病,转化率差异有统计学意义(P=0.002);20例存在Auer小体者中13例转化为急性白血病,62例无Auer小体者中12例转化为急性白血病,两组转化率差异有统计学意义(P=0.000 1);31例小巨核病态改变者中15例转化为急性白血病,51例无小巨核病态改变者中10例转化为急性白血病,转化率差异有统计学意义(P=0.006)。其余病态造血未发现与转化为急性白血病有相关性(均P>0.05)。82例MDS患者中,27例死亡。其中存在原始细胞增多、Auer小体以及小巨核者,其生存时间较短。结论:原始细胞增多、Auer小体、小巨核病态改变与转化为急性白血病及其预后有相关性,对指导预后有一定意义。     

家族聚集性骨髓增生异常综合征/急性髓系白血病家系报道一例并文献复习

目的 探讨家族聚集性骨髓增生异常综合征/急性髓系白血病(MDS/AML)的诊断、临床特点、基因突变及治疗转归.方法 分析1例家族聚集性MDS/AML家系中兄弟患者的骨髓细胞形态学、免疫分型、细胞遗传学、基因突变,对其疗效和转归进行观察,并复习相关文献.结果 先证者在确诊MDS-原始细胞过多难治性贫血Ⅰ型(RAEBⅠ)4个月后进展为AML,其兄在确诊MDS-难治性血细胞减少伴多系病态造血3个月后进展为MDS-RAEBⅡ,生存期分别为5个月和8个月.结论 家族聚集性MDS/AML临床罕见,其诊断需要结合家族史、细胞遗传学、分子生物学等进行综合判断,预后差.     

急性髓系白血病Evi1基因表达的研究

目的 :探讨急性髓系白血病中 Evi1基因表达及意义。方法 :应用 RT- PCR方法检测了 94例急性髓系白血病 (AML ,包括初治 4 9例 ,复发 2 3例 ,缓解 2 2例 )患者及 1 0名正常对照 Evi1基因的表达。结果 :1 0名正常人骨髓单个核细胞中无 Evi1 m RNA的表达。AML 患者 Evi1基因总的阳性表达率为 1 8.1 % (1 7/94 ) ,M5型未见表达 ,其中初治、复发、缓解组的 Evi1基因阳性率分别为2 6 .5 %、1 7.4 %、0 ,初治和复发组差别无显著性 (P=0 .5 5 4 )。M3患者中 Evi1、PML /RARα双阳性组与 PML /RARα单阳性组相比复发率高 (P<0 .0 5 ) ,早期死亡率高。 Evi1阳性的 AML患者多数生存期短。结论 :Evi1基因是一个原癌基因 ,在髓系白血病的发病中起重要作用 ,是髓系白血病预后不良的一个指标。     

由骨髓增生异常综合征转化伴稀有融合基因混合谱系白血病-AFX急性髓系白血病的研究

 目的　对1例由骨髓增生异常综合征（MDS）转化伴稀有融合基因混合谱系白血病（MLL）-AFX的急性髓系白血病（AML）患者进行确诊。方法　骨髓涂片及多重反转录聚合酶链反应（RT-PCR）,检测患者骨髓原始细胞比例及融合基因的表达。结果　患者骨髓单个核细胞中检测到稀有融合基因MLL-AFX的表达。结论　该例患者为MDS转化伴稀有融合基因MLL-AFX的AML,患者预后差。     

TP53突变急性髓系白血病患者异基因造血干细胞移植后接受阿扎胞苷联合西达本胺维持治疗1例

<正>患者男性，28岁。因“反复发热1周，胸痛3天”于2021年7月22日就诊于南方医科大学珠江医院。入院血常规显示：白细胞(WBC)1.36×10⁹/L，中性粒细胞计数(Neu)0.27×10⁹/L，血红蛋白(Hb)60 g/L，血小板计数(PLT)4×10⁹/L。骨髓形态：考虑急性髓系白血病(acute myeloid leukemia,AML)，原始幼稚细胞占29%。骨髓细胞流式细胞学检查：异常表型的原始细胞占25.07%，倾向髓系原始来源。染色体核型：92,XXYY[2]/46,XY[2]。白血病相关融合基因筛查阴性。     

骨髓增生异常综合征bcl-2蛋白表达与细胞凋亡及增殖的关系

目的 :研究骨髓增生异常综合征 (MDS)中 bcl- 2蛋白表达与细胞凋亡及增殖的关系。方法 :以 2 0例 MDS患者、4例急性髓细胞白血病 (AML )患者、4例正常人的骨髓组织为研究对象 ,用免疫组织化学技术 SABC法分别检测 bcl- 2蛋白和增殖细胞核抗原 (PCNA )的表达 ,用 d U TP缺口末端标记 (TU NEL )技术检测细胞凋亡。结果 :MDS、AML、正常人 bcl- 2蛋白表达半定量积分值分别为 2 5 .35± 16 .6 8、6 6 .31± 10 .36、8.2 2± 2 .45 ;MDS、AML与正常对照组凋亡率依次递减 ;AML、MDS与正常对照组 PCNA阳性率依次递减 ;bcl- 2蛋白表达与凋亡负相关 (r=- 0 .6 76 1,P<0 .0 5 )。结论 :bcl- 2蛋白过度表达与细胞凋亡抑制、增殖失控关系密切 ,在 MDS向 AML转化过程中起重要作用     

伴三系病态造血初发性急性髓细胞白血病实验和临床分析

目的 :观察 AML - TMDS在 FAB各亚型的分布、血液学特征和临床化疗效果。方法 :对 AML -TMDS和无 TMDS的 AML 两组 ,进行血象、骨髓细胞形态、骨髓原始细胞计数以及化疗首次完全缓解率的比较。结果 :96例初发 AML 中 ,有 11例为 AML- TMDS(占 11.5 % ) ,见于 M2 、M5 、M6 ,在 M1 、M3中未见到 ;Hb、WBC、BPT无显著性差异 (P>0 .0 5 ) ,骨髓原始细胞计数 AML- TMDS较低 ,两组比较有显著性差异 (P<0 .0 5 ) ,化疗首次完全缓解率无 TMDS的 AML组 (6 2 .7% )较 AML - TMDS组 (46 .5 % )明显降低 (P<0 .0 5 )。结论 :AML - TMDS对化疗不敏感 ,首次完全缓解率低 ,预后不良。     

骨髓增生异常综合征患者外周血循环CD34+细胞计数的临床研究

目的 探讨骨髓增生异常综合征（MDS）患者外周血循环CD34+细胞计数在疾病分型及预后中的意义。方法 流式细胞仪测定16例健康者、40例MDS患者外周血循环CD34+细胞占有核细胞的百分比（简称CD34+细胞百分比）和绝对细胞数。依据WHO MDS诊断标准、染色体核型以及国际预后积分系统（IPSS）将MDS患者分别划分为RA／RARS／RCMD 组和RAEB Ⅰ／RAEB Ⅱ组,染色体良好组、中间组、不良组,中危Ⅰ组、中危Ⅱ组、高危组。结果MDS患者外周血循环CD34+细胞百分比、绝对数分别为0.67％和17.24个／μl,健康者分别为0.03％和1.63个／μl,两者比较差异有统计学意义（P＜0.01）。MDS患者中,RA／RARS／RCMD组CD34+细胞百分比及绝对数分别为0.05％和3.50个／μl,RAEBⅠ／RAEBⅡ组分别为3.09％和81.95个／μl（P＜0.01）;染色体良好组CD34+细胞百分比及绝对数分别为0.05％和3.50个／μl,中间组为1.29％和18.23个／μl,不良组为3.09％和133.10个／μl,随着不良核型的出现,CD34+细胞百分比及绝对数依次增高（P＜0.05）;中危Ⅰ组CD34+细胞百分比及绝对数分别为0.05％和3.50个／μl,中危Ⅱ组为1.57％和35.55个／μl,高危组为8.15％和192.05个／μl,随着IPSS分值的递增,CD34+细胞百分比及绝对数逐渐增高（P＜0.01）。结论 MDS患者外周血循环CD34+细胞计数存在异常增高现象,其计数水平的检测有助于MDS的分型和预后判断。     

Bcl-2基因及其家族Bax,Bcl-Xl和Fas/Apo-l,P16的检测在急性白血病中的临床意义

目的：为了解白血病凋亡正、负反馈网络中的问题与临床的关系，研究了抑制凋亡的基因Ｂｃｌ２及其家族Ｂａｘ，ＢｃｌＸｌ以及诱导凋亡的基因Ｆａｓ／Ａｐｏ１，Ｐ１６。方法：采用细胞免疫组化，ＷｅｓｔｅｒｎＢｌｏｔ，以及ＮｏｒｔｈｅｒｎＢｌｏｔ的方法。结果：发现在ＡＭＬ组和ＡＬＬ组，Ｂｃｌ２抗原表达均明显高于正常（Ｐ＜００１），回顾性分析ＡＭＬＣＲ组其明显低于ＮＲ组（Ｐ＜００１）。蛋白印迹ＣＲ组Ｂｃｌ２表达虽然降低，但和ＮＲ组比较无统计学意义（Ｐ＞００５）。Ｂｃｌ２ｍＲＮＡ的表达ＣＲ组明显低于ＮＲ组（Ｐ＜０．０１）。Ｂａｘ的表达在免疫组化中白血病明显低于正常（Ｐ＜００１），但在ＣＲ组与ＮＲ组，免疫组化，蛋白印迹，ＢａｘｍＲＮＡ的表达，均无差异（Ｐ＞００５）。但ＢｃｌＸｌｍＲＮＡ的表达两组间有明显差异（Ｐ＜００１）。Ｆａｓ／Ａｐｏ１的表达为白血病组低于正常（Ｐ＜００１），但在ＣＲ与ＮＲ组中，免疫组化与蛋白印迹分析均无统计差异（Ｐ＞００５）。Ｐ１６的表达为白血病组低于正常组（Ｐ＜００１），但在ＣＲ组与ＮＲ组中无统计学意义（Ｐ＞００５）。结论：Ｂｃｌ２抗原以及Ｂｃｌ２ｍＲＮＡ，Ｂｃｌ     

Comparisons of prognostic scoring systems for myelodysplastic syndromes: a Korean multicenter study.

We have conducted a multicenter collaborative retrospective analysis to evaluate clinical characteristics and to compare prognostic scoring systems of 149 Korean patients with myelodysplastic syndromes (MDS). The median age of the patients was 53 years (range 17-82 years) with high of the patients being younger than 40 years. Median survival was 22.6 months, and 25 patients (17%) progressed to acute myelogenous leukemia (AML) with a median interval of 6 months (range 1-45 months). Major independent variables assessed by multivariate analysis were FAB subtypes and bone marrow (BM) blast percentages for survival and BM blast percentages for AML transformation. To compare the various scoring systems in the prediction for survival and transformation to AML, FAB, Sanz and Bournemouth scoring systems were applied to all patients, while the international prognostic scoring system (IPSS), Lille and Toyama scoring systems were applied to 91 patients. The Sanz scoring system (P < 0.0001), FAB classification (P < 0.0001), IPSS (P < 0.001), and Toyama scoring system (P < 0.005) were highly predictive for survival showed greater discrimination than that of the other systems. For AML transformation, the IPSS (P < 0.0001), Toyama scoring system (P < 0.0001), FAB classification (P < 0.0001), and Lille scoring system (P < 0.005) successfully discriminated risk groups. Although the prognostic factors and the distribution of age were different from those in Western reports, the IPSS and Toyama scoring system were applicable for predicting survival and leukemic transformation in Korean patients with MDS.     

Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome

BACKGROUND: The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. The regulatory mechanism of endogenous cytokines in circulating platelet counts of thrombocytopenic patients with acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS) is still not clear. METHODS: We measured the serum levels of both thrombopoietic and inflammatory cytokines in peripheral blood and bone marrow samples collected from 52 patients with either AML or MDS along with 35 normal control samples. The levels of thrombopoietin (TPO), interleukin (IL)-11, IL-6, IL-8 and stem cell factor (SCF) were determined by ELISA. RESULTS: Platelet counts in the AML/MDS patients during initial diagnosis, chemotherapy and complete remission were 71.2 +/- 11.6, 47.2 +/- 6.1 and 181.4 +/- 26.3 x10(9)/l, respectively. The median value of TPO in AML/MDS patients during diagnosis was 150.6 pg/ml and increased significantly during chemotherapy (median: 828 pg/ml; p < 0.05) but then decreased following complete remission (median: 221.4 pg/ml). However, these levels were all significantly higher in patients than in normal subjects (p < 0.05, p < 0.05 and p < 0.05; respectively), and no significant change was noted in the levels of IL-11 and SCF during treatment of patients or in normal controls. The level of IL-6 was not detectable in normal serum samples but was markedly increased in the AML/MDS patients (median level during diagnosis: 6.7 pg/ml; chemotherapy: 25 pg/ml; complete remission: 7 pg/ml). The level of IL-8 in patients with AML and MDS was markedly elevated during diagnosis (median: 27.5 pg/ml; range: 0-1,587 pg/ml), but decreased to the level of the normal controls when patients were under chemotherapy or in complete remission. CONCLUSIONS: The endogenous levels of TPO, IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. Our results are consistent with previous mechanistic studies and suggest that TPO and IL-6 may be active mediators of platelet production.     

Factors influencing a second myeloid malignancy in patients with Philadelphia-negative -7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia

The detection of Philadelphia-negative (Ph(neg)) cells with non-random karyotypic abnormalities after tyrosine kinase inhibitor (TKI) therapy of chronic myeloid leukaemia (CML) can be associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). To our knowledge, however, there have been no studies on variables influencing the risk of MDS/AML in patients with specific Ph(neg) karyotypes. We systematically examined studies reporting -7 or del(7q) within Ph(neg) cells in TKI-treated CML patients, and abstracted clinical and cytogenetic data from individual reports into a standardized format for further analysis. Of 53 patients, 43 had Ph(neg) -7 clones [as the sole abnormality (-7(sole)) in 29, or with other clones (-7(dual)) in 14], and del(7q) was present in 10. A total of 16/51 evaluable patients, all with -7, transformed to MDS/AML. Transformation was more frequent (15/16 patients) within 6 months of Ph(neg) -7 detection rather than subsequently (P < 0.0001). At first detection after TKI therapy, Ph(neg) abnormal clones comprised ≥50% of Ph(neg) cells in a greater proportion of patients with -7 than del(7q) (P = 0.035). Upon comparing -7(sole) and -7(dual), the latter was likely to be transient (P = 0.004), and AML was frequently observed with persistent -7 clones (P = 0.03). By logistic regression analysis (n = 36), clone size (P = 0.017), time-to-detection longer than 15 months (P = 0.02), and CML response (P = 0.085) were associated with MDS/AML. Validation of these novel associations in registry-based studies will help develop predictive criteria that define the MDS/AML risk in individual patients.     

肺癌患者外周血细胞CD_(25)、CD_4表达和Apo水平的检测

目的 :研究肺癌患者外周血细胞CD2 5、CD4表达规律和Apo水平。方法 :采用流式细胞术对10 1例肺癌患者外周血细胞CD2 5 、CD3 CD4 表达率和Apo水平进行了检测。并分析了肿瘤转移状况和化疗对上述 3项指标的影响。结果 :肺癌患者外周血细胞CD2 5 和CD3 CD4 率均显著低于正常对照组 (P <0 0 1和P <0 0 5 ) ,Apo显著高于正常对照组 (P <0 0 1)。化疗者的 3项指标均显著高于未化疗者 (P <0 0 1,P <0 0 5和P <0 0 5 ) ;在未化疗患者中 ,有转移者和无转移者之间的CD2 5和CD3 CD4表达率差异均无显著性 (P >0 0 5 ) ,而转移者的Apo却显著高于无转移者 (P <0 0 1) ;在化疗患者中 ,转移者的Apo表达率显著高于无转移者 (P <0 0 1) ,CD2 5 表达率低于无转移者 (P <0 0 5 ) ,而CD3 CD4 二者差异却无显著性 (P >0 0 5 )。结论 :肺癌能抑制患者外周血细胞CD2 5 和CD3 CD4 细胞进一步降低 ,但却引起Apo明显升高。化疗可以提高肿瘤患者CD2 5 、CD3 CD4 和Apo的检出率 ,使机体免疫功能能有所恢复     

新辅助化疗对胃癌细胞凋亡与增殖及其细胞免疫功能的影响

目的探讨新辅助化疗对胃癌患者细胞免疫功能及胃癌细胞凋亡与增殖的影响.方法进展期胃癌患者60例,随机分为3组(每组20例),A组为单纯手术,B组为LF+手术,C组为LOF+手术.分别应用免疫荧光法检测T细胞亚群,核素释放法测定NK细胞活性,TUNEL法和免疫组织化学染色法检测胃癌细胞的凋亡(AI)与增殖(PI)及二者之比(AI/PI).结果B、C组与A组 AI、PI差异具有极显著意义,P<0.01;AI/PI差异有显著意义,P<0.05.化疗前、后及术后3组T细胞亚群的百分率差异无显著意义,P＞0.05.化疗后及术后,B、C组较A组NK细胞活性明显降低,P<0.05,P<0.01.结论新辅助化疗可明显促进胃癌细胞凋亡并抑制其增殖,对手术期患者的T细胞亚群免疫功能无明显影响,但可明显抑制NK细胞活性.     

Induction of gene expression by 5-Aza-2'-deoxycytidine in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) but not epithelial cells by DNA-methylation-dependent and -independent mechanisms.

The methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR, decitabine) has therapeutic efficacy in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Using microarray analysis, we investigated global changes in gene expression after 5-Aza-CdR treatment in AML. In the AML cell line OCI-AML2, Aza-CdR induced the expression of 81 out of 22 000 genes; 96 genes were downregulated (> or =2-fold change in expression). RT-PCR analysis of 10 randomly selected genes confirmed the changes of expression in AML cells. Similar results were obtained with primary AML and MDS cells after treatment with 5-Aza-CdR ex vivo and in vivo, respectively. In contrast, significantly fewer changes in gene expression and cytotoxicity were detected in normal peripheral blood mononuclear and bone marrow cells or transformed epithelial cells treated with 5-Aza-CdR. Interestingly, only 50.6% of the induced genes contain putative CpG islands in the 5' region. To further investigate the significance of promoter methylation in the induced genes, we analyzed the actual methylation status of randomly selected 5-Aza-CdR-inducible genes. We detected hypermethylation exclusively in the 5' region of the myeloperoxidase (MPO) gene. DNA methylation inversely correlated with MPO expression in newly diagnosed untreated AML patients (P< or =0.004). In contrast, all other analyzed 5-Aza-CdR-inducible genes revealed no CpG methylation in the promoter region, suggesting a methylation-independent effect of 5-Aza-CdR.