急性白血病药敏试验与临床缓解的回顾性研究

目的 为寻找快速,经济,简便,可靠的白血病药敏试验方法.方法 回顾MTT法检测的85例初治急性白血病体外药敏试验与临床实际缓解的关系.结果 总阳性符合率为70%,阴性符合率为80%,其中AML阳性符合率73%,阴性符合率70%,ALL阳性与阴性符合率分别为61%,和100%,AML阳性符合率高于ALL,但无统计学差异(P>0.05).AML和ALL组中白血病细胞对一种化疗药物敏感率分别为71%和86%.AML各亚型临床符合率为67%～100%,ALL各亚型为64%～100%,均无统计学差异(P>0.05).分析实验结果与临床实际不符的病例,药敏与CFU—L同步检测的16例中12例有白血病集落自发性生长.结论提示MTT药敏试验可以指导临床用药,是一项值得在基层医院推广的试验.     

急性白血病的基因表达谱分析与亚型分类特征的鉴别

本研究基于生物信息学理论，运用模式识别方法和计算技术，对急性白血病的基因表达谱数据进行分析，研究急性白血病的亚型识别与分类信息基因选取问题。首先去除无关基因，然后利用浮动顺序搜索算法搜索特征空间生成候选特征子集，最后以支持向量机作为分类器进行急性白血病的亚型识别，并以误识率为依据鉴别出了5个包含完整分类信息的基因。实验结果表明，本研究鉴别出的5个信息基因能以100％的正确率准确识别急性白血病亚型。     

基于图卷积神经网络的乳腺癌亚型分类研究

恶性肿瘤分子亚型的准确识别是肿瘤患者个体化诊断、个性化治疗以及预后预测的重要支撑。综合性肿瘤基因组数据库的不断完善和深度学习技术的持续突破,推动了计算机辅助肿瘤分类技术的进一步发展。现有的基于基因表达数据的神经网络亚型分类方法虽然考虑了分子分型的复杂性,但仍然存在忽略基因内在关联性和协同性的问题。为了解决这一问题,本文提出了一种结合分层注意力机制的多层图卷积神经网络乳腺癌亚型分类模型。该模型基于先验的生物学知识构建乳腺癌患者的基因图表示数据集,训练出一种新的端到端的多分类模型,能够对乳腺癌分子亚型进行智能识别,并且在乳腺癌分子亚型的分类工作上表现出了很好的识别性能。相较于原始的图卷积神经网络以及两个主流的图神经网络分类算法,该模型在7分类任务中的准确率、加权F1分数、加权召回率、加权精确率分别达到了0.851 7、0.823 5、0.851 7、0.793 6,在4分类任务中则分别达到了0.928 5、0.894 9、0.928 5、0.865 0,具有明显的优势。此外,本文方法相较于最新的乳腺癌亚型分类算法,同样获得了最高的分类准确率。综上,本文所提模型或可作为一种辅助诊断技术为未来...     

CD117在急性白血病中的表达及临床意义

目的探讨CD117在急性白血病中的表达及其临床意义。方法应用CD45/SSC设门,直接荧光标记法,经流式细胞术对73例急性髓系白血病（AML）和47例急性淋巴细胞白血病（ALL）进行CD117的检测。结果对照组、ALL及AML3组CD117的表达阳性率差异有统计学意义（χ2=41.681,P﹤0.01）。AML组CD117的表达阳性率（58.9%）明显高于对照组（0）及ALL组（8.5%）。CD117/CD34的共表达率ALL组明显低于AML组（4.3%vs45.2%,P﹤0.05）。AML组CD117＋患者的CR率为60.5%,CD117-患者为76.7%,两者比较差异无统计学意义（P〉0.05）;而CD117＋/CD34＋患者的CR率为54.5%,明显低于CD117-/CD34-患者的CR率（88.2%,P﹤0.05）。结论 CD117可作为辅助诊断AML的髓系标志抗原,CD34＋/CD117＋可作为进一步排除ALL的指标。CD117＋/CD34＋可能是AML中一类预后不良的特殊亚型,可以作为AML预后判断的指标之一。     

急性淋巴细胞白血病患者BAALC基因表达水平也许有临床意义

目的研究急性淋巴细胞白血病（ALL）患者脑和急性白血病细胞胞浆（BAALC）基因的表达水平及其临床意义。方法57例经细胞形态学、组织化学染色及流式细胞术免疫学分型确诊的ALL患者,其中男性35例,女性22例;中位年龄23（14～66）岁。FAB分型L19例。L245例,L33例。建立实时荧光定量PCR检测BAALC基因表达的技术,并定量检测57例初发ALL患者BAALC基因的表达水平及进一步分析其与临床疗效的关系。结果57例初发ALL患者BAALC基因表达水平显著高于对照组。FAB各亚型中BAALC基因表达水平差异无统计学意义（P〉0．05）,BAALC基因表达水平的高低与初发AI上患者的免疫表型具有显著性相关．T—ALL患者和伴有髓系抗原表达ALL患者BAALC基因表达水平显著高于B—ALL（P〈0．05）和不伴有髓系抗原表达ALL患者（P〈0．01）。ALL中BAALC基因表达的水平与外周血白细胞计数（WBC）、血红蛋白（Hb）、血小板计数（Plt）及骨髓白血病细胞比例无明显相关性（P〉0．05）。BAALC基因高表达ALL患者的完全缓解率（73．3％）同低表达组f81．0％）比较差异无统计学意义（P〉0．05）,但BAALC基因高表达患者1年复发率（81．8％）明显高于低表达组（44．1％）（P〈0．05）。结论BAALC基因高表达提示可能是ALL患者一个不良预后因素,检测ALL患者BAALC基因表达水平可能有助于指导治疗。     

急性髓细胞白血病患者CD56抗原表达与MDR1基因表达量的关系研究

目的 研究初治急性髓细胞白血病(AML)患者CD56抗原表达与多药耐药(MDR)1基因表达量的关系,探讨CD56抗原表达与MDR1基因表达量在AML耐药中的作用及相互关系.方法 采用流式细胞术(FCM)和建立实时荧光定量PCR技术分别检测79例AML患者CD56抗原表达及MDR1基因表达水平并分析两者之间的关系及临床意义.结果 24.1%AML患者表达CD56抗原,FAB亚型中M5 AML患者表达阳性率高于其他亚型.遗传学危险度分级高危组患者CD56抗原表达阳性率显著高于中危组(P<0.01),伴t(8:21)AML患者CD56抗原表达阳性率(57.1%)显著高于其他低危组AML(P<0.05).CD56抗原表达阳性初治AML患者MDR1基因表达水平显著高于表达阴性患者(P<0.001).MDR1基因高表达且CD56抗原阳性AML组的CR率(58.8%)显著低于MDR1基因低表达且CD56表达阴性组(89.2%,P<0.01).结论 AML患者CD56抗原表达与MDR1基因表达水平存在相关性;同时定量检测MDR1基因表达及CD56抗原表达更有助于判断预后.     

CD64在急性白血病免疫分型中的意义

目的探讨CD64在急性白血病免疫分型中的意义。方法应用直接荧光标记法,经流式细胞术对116例急性髓系白血病(AML)和70例急性淋巴细胞白血病(ALL)进行免疫表型的检测。结果 AML组CD64的表达阳性率明显高于ALL组(41.4%vs 2.9%,P<0.01)。CD64在M5和M4的表达阳性率最高,分别为77.1%和55.6%。CD64的阳性表达率在M0(0)、M1(0)、M2(7.9%)明显低于M3(47.1%)、M4与M5(P<0.01)。各亚型CD64阳性病例中,M4、M5的CD64阳性细胞表达率分别为(62.5±24.7)%、(68.7±25.9)%,均明显高于M2(28.3%±5.7%)、M3(34.3%±6.3%)(P<0.01)。CD64对诊断AML的灵敏度优于CD14,其特异度优于CD117、CD33及CD13。虽然CD64诊断M4\M5的特异度较CD14稍差(82.5%vs 100%),但是灵敏度高于CD14(69.8%vs 41.5%)。结论 CD64可作为辅助诊断AML的髓系标志抗原,有助于提高M4/M5的检出率及其与其他AML亚型的鉴别诊断。     

基于遗传算法的基因表达数据的K-均值聚类分析

聚类算法在基因表达数据的分析处理过程中得到日益广泛的应用.本文通过把 K-均值聚类算法引入到遗传算法中,结合基因微阵列的特点,来讨论一种基于遗传算法的K-均值聚类模型,目的是利用遗传算法的全局性来提高聚类算法找到全局最优的可能性,实验结果证明,该算法可以很好地解决某些基因表达数据的聚类分析问题.     

基于相对风险的肿瘤基因差异表达分析

目的寻找与肿瘤相关的基因诊疗中差异表达基因提取的方法。方法将基因表达谱数据进行预处理,采用相对风险方法筛选出差异表达基因特征子集,计算其样本间距离,然后对特征基因加权排序和过滤冗余基因,最后应用分类器对卵巢癌基因数据集进行分析,测试该方法的有效性。结果选取20维特征基因,进行分类测试,当特征基因为3～5、7和12～20维时,分类准确率可以达到100%,假阳性率可以达到0,表现出较好的可靠性,能够有效地将2个样本类型分开。结论经分类器测试证明,分类精度高,效果优于使用传统的基因差异表达分析方法。     

基于被动听觉ERP范式的慢性意识障碍患者个体评估研究

近年来,大脑功能检测技术逐渐应用于意识障碍(DoC)患者的意识水平评估,以期降低仅依靠临床主观行为量表评估的误诊率。其中,被动听觉事件相关电位(ERPs)范式下诱发的N1和失匹配负波(MMN)成分被认为是反应DoC患者意识水平的关键脑功能指标,但目前仍局限于组别层面的统计分析结果,其在DoC患者个体水平的评估效能尚待挖掘。根据N1和MMN成分的特性,提出了一种适用于被动听觉ERPs范式下DoC患者个体评估的深度学习算法。该方法引入了特征融合的数据扩增策略,即在单被试数据中随机抽取不同类型的试次进行空间级联形成新的融合样本,并结合EEGNET深度学习算法实现自动化特征提取和分类识别。在包含132名被试的单试次数据集上进行测试。对健康被试(38名),微意识状态(40名)和植物状态(54名)患者进行三分类评估。统计分析结果表明,该样本融合策略可显著提升模型分类表现,并在单被试融合样本数量扩增至1 000时模型取得样本水平75.14%的平均分类准确率,以及被试水平83.00%的平均分类准确率,83.79%的精确率和84.02%的召回率。所提出的深度学习框架可有效克服传统方法中存在的个体评估能力不强的问题,为DoC患者个体评估提供新的研究思路。     

Impact of cellular CD71 (transferrin receptor 1) expression in Egyptian acute leukemia: correlation with clinicopathologic features

Cellular transferrin receptor 1 (CD71) has been identified as a proliferation marker. Inferior outcome with higher expression was observed in many solid tumors. This study objected to assess the expression of CD71 in patients with acute leukemia and to address its prognostic significance and relations to clinicopathologic features. The study included 34 acute myeloid leukemia (AML) and 64 acute lymphoblastic leukemia (ALL) newly diagnosed cases from Mansoura Oncology Center. CD71 was analyzed on blast cells by flow cytometry. CD71 expression was significantly elevated in both AML and ALL. Antigen expression apparently increased in T-ALL, while in AML there was a trend toward a gradual increase of antigen expression in relation to maturation evidence of myeloid subtypes. CD71 expression correlated positively with total leukocyte count in ALL cases and negatively with platelet count in AML cases. In ALL, higher CD71 expression was associated with higher relapse rate and was an independent prognostic factor of overall survival (HR 1.8; 95 % CI 1.2–4.1). In conclusion, CD71 is overexpressed in acute leukemia; it predicts adverse clinical outcome in ALL. In addition, CD71 antagonism could be a possible therapeutic target in acute leukemia.     

Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy

Resistance to chemotherapy is a major impediment to the successful treatment of acute leukemia (AL). Expression of genes involved in drug resistance and apoptosis may be responsible for this. This study aimed to investigate the expression of drug resistance (MDR1, MRP1, LRP, BCRP, GSTP1, DHFR) and apoptotic genes (p53, BCL-2, Survivin) in adult acute leukemias and compare them with clinical and hematological findings and response to induction chemotherapy. Eighty-five patients with AL [45 with acute myeloid leukemia (AML) and 40 with acute lymphoblastic leukemia (ALL)] were used as a study group. Real-time PCR results showed that expression level of MDR1 was significantly higher in AML whereas expression of DHFR, BCRP and Survivin was significantly higher in ALL patients. In AML, significant correlation was observed between LRP and MRP1 (r(s)=0.44, p=0.016), LRP and DHFR (r(s)=0.41, p=0.02), MDR1 and BCL-2 (r(s)=0.38, p=0.03). Expression of GSTP1 and LRP correlated with high white blood count (p=0.03 and p=0.03) and BCL-2 with high peripheral blast count (p=0.009). MDR1 expression was significantly associated with the expression of immature stem cell marker CD34 (p=0.002). In ALL, significant association was found between LRP gene and female sex (p<0.0001), LRP and B-ALL patients (p=0.04) and LRP and BCR/ABL positive patients (p=0.004). High expression of MDR1 and BCL-2 in AML and MRP1 gene in ALL was associated with response to induction chemotherapy (p=0.001, p=0.02 and p=0.007 respectively). These results showed the potential clinical relevance of MDR1, MRP1 and BCL-2 in adult patients with acute leukemia in the context of induction chemotherapy.     

急性髓细胞性白血病M2患者形态学及免疫学分型与融合基因染色体检查的价值

背景：传统的形态学分型法仅能使70%左右的急性白血病得以准确分型,单纯的FAB分型已远远不能满足临床需要。 目的：评价形态学、免疫分型、融合基因、染色体检查在急性髓细胞性白血病(M2)中的诊断价值及预后意义。 方法：选择新疆医科大学第一附属医院收治的急性髓细胞性白血病患者M2型76例,男40例,女36例。用反转录-聚合酶链反应技术检测AML1/ETO融合基因的表达、R带法进行染色体核型分析、流式细胞仪免疫分型检测,应用形态学和免疫分型、融合基因、染色体检查,并持续观察,定期检查血象等相关检查,由是否能明确诊断或协助诊断,对复发有无相关检查预测性来分析其诊断价值及预后影响因素。 结果与结论：76例患者中有形态学不易分类的6例患者,结合免疫分型、融合基因及染色体检查可明确,单纯髓系抗原表达较伴有干祖系抗原表达缓解率高,CD19抗原可与部分急性髓系白血病有交叉表达,且有交叉表达的有较好的预后,伴有CD7抗原表达7例均完全缓解,可能更倾向于分化成熟的细胞,具有单纯t(8,21)、融合基因阳性者预后较佳,完全缓解率高。提示形态学、免疫学分型结合融合基因、染色体检查可提高急性白血病M2的诊断准确性、判断预后。     

Low incidence of TEL/AML1 fusion and TEL deletion in Korean childhood acute leukemia by extra-signal fluorescence in situ hybridization

TEL/AML1 fusion in acute leukemia results from cryptic translocation of chromosome 12 and 21, the presence of which suggests a favorable prognosis. The incidence of TEL/AML1 fusion in B-lineage ALL is approximately 25%, but the incidence in Korea has not yet been reported. To investigate the incidence of TEL/AML1 fusion and TEL deletion, bone marrow specimens from 77 Korean children with newly diagnosed acute leukemia were analyzed by FISH. We applied extra-signal FISH to discriminate a true TEL/AML1 fusion from a false-positive fusion signal. To determine the cut-off value of the TEL/AML1 fusion signal, 20 normal bone marrow specimens and 28 normal peripheral blood specimens were also analyzed. The frequency of patients with TEL/AML1 fusion was 13.3% (4 cases) among 30 B-lineage ALL and 9.5% among 42 ALL. One TEL/AML1 fusion-positive patient was also found among 4 acute biphenotypic leukemias. TEL/AML1 fusion was not found in any samples from patients with T-lineage ALL or AML. The incidence of TEL deletion was 6.7% (2 cases) among 30 B-lineage ALL and 4.8% among 42 ALL. The incidences of TEL/AML1 fusion and TEL deletion in Korean children with acute leukemia appear to be lower than those in other countries, suggesting a racial difference.     

Utility of white blood cell suspect flags and histogram pattern in the detection of acute leukemia by Advia-60 automated hematology analyzer

Blood samples from patients with acute leukemia, when analyzed with automated hematology counters, tend to introduce inaccuracies in the automated differential count and can cause diagnostic confusion without providing definite clues to the presence of abnormal cells. We designed this study to assess the utility of white blood cell (WBC) flags and histogram pattern generated by Advia-60 automated hematology analyzer in the recognition and categorization of acute leukemia. Data printouts of 31 newly diagnosed cases of acute leukemia, 22 with acute myeloid leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL) were reviewed. All cases of AML and ALL generated the WBC suspect blastflag M2 associated with two of the non blast suspectflags G1 and G2. Among the cases of AML, 95.5% of the WBC histogram patterns were definitive of the presence of abnormal cells and were indicative of the myeloid nature of cells. Only 44.4% of the histograms in the cases of ALL could be definitive of the presence of abnormal cells and 33.3% were indicative of their lymphoid nature. Significantly, 55.5% of the histograms in ALL were normal. The false positives for both AML and ALL were 10.5% when only WBC flagging was considered and were reduced to 0.05% when the flags were combined with histogram patterns for interpretation. Combined flagging and histogram recognition can be of aid in identifying cases of acute leukemia and the morphologist can then assess these samples further. This ensures that cases of acute leukemia, especially in high output laboratories, are not inadvertently missed.     

Electron microscopic studies on the occurrence of activated neutrophils in peripheral blood of children with acute leukemias

Peripheral blood (PB) cells are examined to assess cellular maturity and the degree of bone marrow abnormality in children with acute leukemias. During the ultrastructural assessments of PB cells in these children, we noted a frequent occurrence of activated neutrophils. This phenomenon had not been reported previously. We here report for the first time the identification of activated neutrophils in PB of children with acute leukemias. To examine the impact of activated neutrophils, we compared two groups of children including 18 with acute lymphoblastic leukemia (ALL) and 7 with acute myelogenous leukemia (AML) by an ultrastructural leukocyte count method. Many cases (50%) showed more than 30% activated neutrophils per total neutrophil count in PB. Activated neutrophils were elongated or amoeboid-shaped cells ranging from 13-18 microns in greater diameter with a decreased number of granules in the cytoplasm. A significantly higher rate of activated neutrophils was observed in ALL as compared with AML (median: 42.97% vs. 10.64%). Non-leukemic hospitalized (n =3) and healthy (n = 3) control cases showed a median rate of 3.32% activated neutrophils in PB. These findings reveal that a significantly high rate of activated neutrophils occurs in PB of children with ALL which may be exploited in the diagnostic assessment of children with acute leukemias.