一例急性巨核细胞性白血病和Down氏综合征的c-sis基因表达

新鲜巨核细胞是否有c-sis基因表达尚未阐明,作者发现一例10个月的巨核细胞白血病伴Down氏综合征的病孩的新鲜巨核细胞和建立的细胞株上有c-sis表达。作者用快速印迹法,此白血病的各临床阶段的巨核细胞中均有c-sis表达,而淋巴细胞和其他白血病细胞均无c-sis表达。复发时,外周血及骨髓细胞中的c-sis mRNA水平较治疗前高出5倍以上。另一例5个月的急性巨核细胞性白血病的细胞也有c-sis mRNA表达。将患者的原始细胞培养建立巨核细胞株(CMK)。这种巨核细胞与原来的原始细胞的染色体同样表现为der(17)t(11∶17)。在     

急性巨核细胞白血病:临床、血液学和免疫学特点

FAB将急性巨核细胞白血病(AMKL)定为M7型。作者研究了1982-1986年就诊的409例急性白血病中的28例AMKL的特点。方法:(1)细胞形态学和组织化学研究,包括非特异性脂酶,α萘酚醋酸脂酶(ANAE)及α萘酚丁酸脂酶(ANBE);(2)免疫学标志,包括抗糖蛋白单克隆抗体,抗-GPⅢa(C17)及抗-GPⅡb/Ⅲa(FMC24,J15)等。结果:(1)28例AMKL中,既往患骨髓增殖性疾病,骨髓增生异常综合征,急性非淋巴细胞白血病及继发性白血病者分别占10,3,14与1例;(2)患者血红蛋白平均为8.8±2g/dl,50%患者白细胞计数<7×10~9/L,血小板正常或增高;(3)既往患白血病的AMKL患者14例,平均存活期为7.6个月,其中3例采用急性粒细     

急性淋巴细胞白血病患者骨髓细胞中CCL2 mRNA的表达

背景:临床工作中希望能够根据骨髓CCL2表达对急性淋巴细胞白血病患者进行危险分层和预后判断。目的:观察急性淋巴细胞白血病患者骨髓细胞中CCL2 mRNA的表达情况。方法:初诊50例急性淋巴细胞白血病患者为实验组,30例非血液肿瘤患者为对照组。初诊急性淋巴细胞白血病患者化疗2个疗程后按疗效分为完全缓解组43例,未完全缓解组7例。实验抽取研究对象骨髓5mL,采用半定量聚合酶链反应法检测CCL2 mRNA表达。结果与结论:①初诊急性淋巴细胞白血病组CCL2 mRNA表达水平明显高于对照组(P<0.05);完全缓解组CCL2 mRNA水平明显低于未完全缓解组(P<0.01);完全缓解组治疗后CCL2 mRNA表达水平明显低于治疗前(P<0.01)。未完全缓解组治疗2个疗程后CCL2 mRNA表达水平无明显下降(P>0.05)。②前B-急性淋巴细胞白血病患者骨髓CCL2 mRNA表达水平明显高于普通B及T系急性淋巴细胞白血病患者(P<0.05)。初诊时白细胞≥50×109L-1急性淋巴细胞白血病患者CCL2 mRNA表达水平明显高于白细胞<10×109L-1及10×109L-1≤白细胞<50×109L-1组(P<0.05),10×109L-1≤白细胞<50×109L-1组明显高于白细胞<10×109L-1组(P<0.01)。结果表明急性淋巴细胞白血病患者骨髓细胞能分泌CCL2,骨髓CCL2 mRNA表达水平与患者初诊时的白细胞计数及免疫分型有一定的关系,在一定程度上能反映患者的近期疗效。     

急性白血病患者周期蛋白D1mRNA表达及其临床意义

目的　检测急性白血病患者周期蛋白 (cyclin)D1mRNA的表达 ,并探讨其与临床的关系。方法　采用逆转录 聚合酶链反应 (RT PCR)技术检测 6 5例急性白血病患者及 5名正常人骨髓细胞cyclinD1mRNA。结果　正常骨髓未检测到cyclinD1mRNA表达 ;急性白血病患者阳性率 2 6 2 % ,急性淋巴细胞白血病与急性非淋巴细胞白血病之间差异无显著性 ;复发组患者的cyclinD1mRNA阳性率 (6 3 6 % )明显高于初治组 (2 1 4% )及缓解组 (8 3% )。结论　急性白血病患者中有cyclinD1mRNA过度表达的情况 ,且与临床复发关系较为密切。     

急性巨核细胞白血病一例诊断分析

巨核细胞白血病(AMKL)是急性白血病中一种少见的类型。发病多为幼儿及青壮年,此病病情凶险,疗效不佳。近年来随着对巨核超微细胞化学及免疫细胞化学的深入研究,诊断技术不断改进与提高,对AMKL的认识逐渐加深,本病诊断率在提高。但是以往文献报道的AMKL大多数只是进行文字描述,或强调原幼巨核细胞缺乏特异的形态特征,与急性淋巴细胞白血病、急性粒细胞白血病、急性单核细胞白血病的原始细胞难以区别,只能利用电镜观察血小板过氧化物酶反应(PPO)和血小板特异的单克隆或多克隆抗体标记才能识别巨核细胞。本病例巨核细胞形态典型,我们将其…     

癌基因c-erbB在骨髓增生异常综合征(MDS)骨髓细胞中的表达及其意义

采用生物素标记探针原位杂交(ISH)对MDS13例、急非淋(ANLL)10例和良性血液病8例,共31例患者骨髓细胞c-erbB表达进行了观察,同时对c-myc表达作了比较,发现8/13例MDSc-erbB mRNA过高表达,10/13例MDSc-myc mRNA过高表达;在10例ANLL病人中,仅1例c-erbB mRNA高表达,7例c-myc mRNA高表达;8例良性血液病两种癌基因均无表达,1例在2月内由RA发展到RAEB-T患者其c-erbB和c-myc表达明显增强。用ISH发现癌基因过度表达比临床常规形态学确诊提前8周,提示c-erbB和c-myc转录增强对MDS急剧演变有预后意义,c-erbB参与MDS发生与发展过程。     

急性淋巴细胞白血病患者骨髓细胞中CCL2 mRNA的表达

背景：临床工作中希望能够根据骨髓CCL2表达对急性淋巴细胞白血病患者进行危险分层和预后判断。目的：观察急性淋巴细胞白血病患者骨髓细胞中CCL2 mRNA的表达情况。方法：初诊50例急性淋巴细胞白血病患者为实验组,30例非血液肿瘤患者为对照组。初诊急性淋巴细胞白血病患者化疗2个疗程后按疗效分为完全缓解组43例,未完全缓解组7例。实验抽取研究对象骨髓5mL,采用半定量聚合酶链反应法检测CCL2 mRNA表达。结果与结论：①初诊急性淋巴细胞白血病组CCL2 mRNA表达水平明显高于对照组（P〈0.05）;完全缓解组CCL2 mRNA水平明显低于未完全缓解组（P〈0.01）;完全缓解组治疗后CCL2 mRNA表达水平明显低于治疗前（P〈0.01）。未完全缓解组治疗2个疗程后CCL2 mRNA表达水平无明显下降（P〉0.05）。②前B-急性淋巴细胞白血病患者骨髓CCL2 mRNA表达水平明显高于普通B及T系急性淋巴细胞白血病患者（P〈0.05）。初诊时白细胞≥50×10^9L^-1急性淋巴细胞白血病患者CCL2 mRNA表达水平明显高于白细胞〈10×10^9L^-1及10×10^9L^-1≤白细胞〈50×10^9L^-1组（P〈0.05）,10×10^9L^-1≤白细胞〈50×10^9L^-1组明显高于白细胞〈10×10^9L^-1组（P〈0.01）。结果表明急性淋巴细胞白血病患者骨髓细胞能分泌CCL2,骨髓CCL2 mRNA表达水平与患者初诊时的白细胞计数及免疫分型有一定的关系,在一定程度上能反映患者的近期疗效。     

急性巨核细胞白血病5例临床分析

目的：探讨急性巨核细胞性白血病（AMKL）的细胞免疫学诊断和化疗疗效。方法：用流式细胞术单克隆抗体直接免疫标记检测白血病细胞表达相关抗原表达，短期培养法与直接法G显带检测染色体组型；TA或HA方案化疗。结果：5 AMKL均表现CD42和CD41的高表达，其中2种伴CD13和CD33高表达，TA方案化疗达完全缓解1例，结论：流式细胞单克隆抗体直接免疫标记白血病细胞表达相关的抗原表达可以确定AMKL的诊断，TA或HA方案辅以强有力支持治疗AMKL可以获得完全缓解。     

c-myc、c-myb基因在白血病骨髓基质细胞中的表达及相关性研究

本研究检测分析c-myc、c-myb原癌基因在白血病细胞和骨髓基质细胞(BMSC)中的表达及其相关性。用逆转录聚合酶链反应(RT-PCR)技术定量分析原癌基因c-myc、c-myb的表达水平,通过流式细胞术分析白血病细胞和BMSC的膜表面抗原,同时采用染色体显带技术分析细胞核型。结果表明:①c-myc、c-myb基因在白血病细胞及其BMSC中均有一定的表达,尤其是在染色体异常的白血病细胞中高表达,其均值分别为1.15±0.38和1.03±0.48,与对照组比较均具有统计学差异(P<0.05);在染色体异常的BMSC中其均值分别为2.08±0.82(P<0.05)和1.46±0.29(P<0.05);②在白血病细胞和BMSC中,c-myc mRNA、c-myb mRNA的表达水平均与血小板计数具有相关性;③在不同预后组中,c-myc mRNA、c-myb mRNA表达呈线性相关;④在白血病细胞及急性组BMSC中原癌基因c-myc、c-myb的表达存在正相关;⑤白血病细胞中c-myc的表达量分别与BMSC中c-myc、c-myb的表达量有相关性。结论:在白血病中降低c-myc或c-myb原癌基因的表达水平可能成为治疗白血病的一种治疗方案。     

链亲和素-胶体金原位杂交研究急性白血病的髓过氧化物酶基因表达

用链亲和素-胶体金原位杂交(ISH-SAG)检测了87例急性白血病、7株白血病细胞系和7例正常骨髓细胞的髓过氧化物酶(MPO)的基因表达。结果发现,7例正常骨髓细胞几乎不表达MPO mRNA;粒(单核)细胞系和急性髓性白血病(AML)细胞不同程度表达MPO mRNA;淋巴细胞系和急性淋巴细胞白血病(ALL)细胞不表达MPOmRNA;7例难分类急性白血病(UAL)中,4例表达MPO mRNA并对髓系抗原阳性;诊断为极低分化的AML;2例只表达免疫球蛋白重链基因,考虑为早期B细胞ALL;1例无任何细胞标志,考虑为急性未分化细胞白血病。上述结果表明,用ISH-SAG检测MPOmRNA敏感性高,特异性强,为确诊AML和区分ALL提供了一个更为有用的新手段,特别对识别停滞在细胞分化早期的AML意义更大。     

Ras oncogene mutation in multiple myeloma

The frequency of ras (H-, K-, and N-ras) and c-myc oncogenes was investigated in multiple myeloma (MM). By means of the polymerase chain reaction (PCR)/oligonucleotide hybridization method, DNA from 56 tumor biopsies was analyzed for the presence of activating mutations involving codons 12 and 61 of the H-, K-, and N-ras genes and codon 13 of the N-ras gene. Mutations, involving the N- or K-ras genes, were detected in 18 of 56 (32%) cases of which 12/43 (27%) were at diagnosis and 6/13 (46%) were after treatment. In some cases, multiple mutations affecting different ras alleles were detected. Direct nucleotide sequence analysis of PCR products indicated that a more heterogeneous nature of the base pair changes than previously shown for other tumors along with a preferential involvement of N-ras codon 61. The heterogeneity of MM cases with respect to the presence of ras oncogenes prompted an analysis of possible correlations with different clinico-pathologic characteristics of MM from which a correlation between the presence of ras oncogenes and a partial or complete lack of response to therapy emerged. The frequency of activating rearrangements or mutations of the c-myc gene were studied by Southern blot analysis and PCR sequencing, respectively. However, contrary to previous reports involving mostly MM cell lines, no structural alterations of the c-myc gene were found. These results indicate that ras, but not c-myc, oncogenes are activated in vivo in MM cells, representing the first oncogene alteration that has been associated at appreciable frequency with this type of malignancy. While the mechanism of occurrence and biological role of ras activation in MM remains to be elucidated, the preliminary correlations observed in this study between the presence of ras oncogenes and poor therapeutic response suggest that further investigations of the possible prognostic significance of these alterations are necessary.     

Down syndrome with myelodysplasia of megakaryoblastic lineage.

The association between Down syndrome and acute myelogenous leukemia (AML) has been well documented. AML in Down syndrome is usually a specific type of megakaryoblastic leukemia (M7, AMKL). A myelodysplastic syndrome generally precedes this malignancy. Down syndrome patients with AMKL have a much better prognosis than other children with AML. A case study of a 22-month-old female with Down syndrome and myelodysplastic syndrome of a megakaryoblastic lineage is presented here. Upon admission to a pediatric hematology/oncology clinic, flow cytometry results reported a distinct population of phenotypically abnormal myeloblasts expressing myeloid antigens and the immature cell markers. The patient was placed on a national research group study and began chemotherapy treatment. To date she has received two courses of cytarabine (ara-c) and daunorubicin therapy, which were tolerated well, and is awaiting her third course. Her blood counts stabilize for a while after treatments and her prognosis is good.     

Platelet-derived growth factor in idiopathic pulmonary fibrosis.

Fibrosis is a complex process involving an inflammatory reaction, fibroblast proliferation, and abnormal accumulation of interstitial collagens. Mononuclear cells are usually present in lung fibrosis. Activated monocytes and macrophages in culture have been shown to produce several growth factors including platelet-derived growth factor (PDGF). PDGF is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells and a stimulator of collagen synthesis. We have studied the expression of c-sis/PDGF-2 mRNA in lung tissues derived from five patients with idiopathic pulmonary fibrosis (IPF) and from four control individuals without IPF. Northern blot analysis of specimens obtained from four patients with IPF revealed the expression of the c-sis/PDGF-2 protooncogene. A control lung tissue without IPF did not express the c-sis protooncogene. In situ hybridization extended these studies demonstrating the expression of the c-sis mRNA in the five specimens with IPF but not in the four control specimens without IPF. The expression of c-sis mRNA was localized primarily in the epithelial cells. Invading alveolar macrophages also expressed c-sis mRNA. The expression of c-sis mRNA was accompanied by the expression of PDGF-like proteins in lung specimens with IPF but not in control lung specimens. These findings demonstrate the in vivo expression of the c-sis/PDGF-2 protooncogene and the production of PDGF-like proteins in the epithelial cells and macrophages of the fibrotic tissue. This localized and sustained production of PDGF-like mitogen may constitute an important contributing factor in the abnormal fibroblast proliferation and collagen production, events associated with pulmonary fibrosis.     

同基因骨髓混合H-2半相合异基因骨髓移植的抗白血病效应实验研究

为了诱发自体骨髓移植(ABMT)后的移植物抗白血病(GVL)效应,提高患者的长期无病存活,研究了同基因混合H-2半相合异基因骨髓移植(MBMT)后的GVL效应以及移植物抗宿主病(GVHD)的耐受情况。通过混合脾细胞移植对新生小鼠GVHD的作用和MBMT对成年小鼠GVHD的活体观察,证实受体小鼠接受亚致死剂量放射后行同基因骨髓移植时,能够耐受1/6有核细胞量的H-2半同基因骨髓而不发生或发生轻度GVHD。比较观察混合1/6有核细胞H-2半同基因的同基因BMT的抗白血病效应。结果显示,单用同基因BMT者移植后2周皆死亡,混合组5周后仅2只死亡,预计生存率为66％,存活小鼠未观察到明显的GVHD,单纯照射组及L615白血病细胞接种组者1周内全死亡,照射后未接种白血病细胞而行同基因BMT者5周仅1只死亡,提示接受1/6量H-2半同基因骨髓细胞的同基因骨髓移植有显著的抗白血病效应(P<0.01),而不发生GVHD。这一研究为临床ABMT后诱导GVL效应,提供了一个新的途径。     

Acute megakaryoblastic leukemia in Down syndrome, following thrombocytopenia with antiplatelet antibody

We report a case of acute megakaryoblastic leukemia (AMKL) with antiplatelet antibody in a boy with Down syndrome. When the patient was admitted, his platelet count was 1.3 X 10(4)/mm3 and antiplatelet antibody in the plasma was detected. Two months after admission, blasts, which showed positive reaction to both antiplatelet monoclonal antibody and platelet peroxidase, increased.     

Induction of c-ets and c-fos gene expression upon antigenic stimulation of a T cell hybridoma with inducible cytolytic capacity

Expression of cellular oncogenes was studied in a T cell hybridoma that undergoes cytolytic activation when stimulated by specific antigen or by anti-Thy-1 antibody. The activation occurs without induction of hybridoma proliferation, providing a model to examine oncogene expression during functional differentiation of lymphocytes. We found that c-fos and c-ets-1 mRNAs were transiently induced at high levels in the hybridoma 30 min and 4 h after stimulation, respectively. c-myc and c-ets-2 oncogenes were constitutively expressed in the hybridoma and their mRNA levels were unaffected during 4 h of stimulation, although c- myc expression was reduced in the later stage of stimulation. Inhibitors of T cell activation, cyclosporin A and anti-LFA-1 antibody, blocked the induction of c-fos and c-ets-1 mRNAs without reducing the levels of c-myc and c-ets-2. The results indicate that the functional activation of the CTL hybridoma is associated with induction of c-fos and c-ets-1 genes.