180例慢性粒细胞白血病骨髓染色体畸变及意义

目的　研究骨髓染色体畸变与慢性粒细胞白血病 (慢粒 )不同病期的相关性及其临床意义。方法　采取新鲜骨髓 ,进行短期培养 (48小时或 12小时预加秋水仙素培养 )制备染色体标本 ,分析 180例慢粒患者慢性期、加速期、急变期骨髓染色体的变异情况。结果　 180例慢粒患者 ,其中 16 4例Ph染色体阳性 (Ph ) ,占 91 1% ;16例Ph染色体阴性(Ph - ) ,占 8 9%。慢性期 133例Ph ,占总数的 73 9% ;加速期 9例Ph ,占总数 5 0 % ;急变期 2 2例Ph ,占总数12 2 %。 16 4例Ph 慢粒患者中 2 5例 (15 2 % )伴有额外染色体异常 ,其中慢性期占 4 2 7%、加速期占 2 4 %、急变期占8 5 3%。结果表明随着病情的进展 ,Ph 阳性率明显增高 ,其它染色体异常率也明显增高。结论　骨髓染色体畸变与慢粒白血病的病程进展、疾病预后有着十分重要的相关性 ,随着病情的演变 ,骨髓染色体畸变趋于复杂化。进行染色体分析对临床诊断及治疗慢粒具有十分重要的指导意义。     

慢性粒细胞白血病患者染色体检查及预后意义探讨

目的探讨慢性粒细胞白血病(CML)患者染色体变化的有关特点及预后意义.方法染色体制备采用骨髓细胞短期培养法,应用G、R显带技术对85例CML患者的骨髓细胞进行遗传学分析.结果 85例CML患者中,78例检出典型Ph染色体,占91.76%,3例为变异Ph易位,占3.53%,4例Ph染色体阴性,占4.71%,10例核型呈嵌合状态,13例出现附加染色体异常,主要为 8,i(7), Ph, 22, 12等,其中9例为加速和急变期患者,占64.29%.结论 CML是一种高度异质性疾病,非随机的附加染色体异常与患者临床分期高度相关.CML患者进行染色体分析对于疾病的诊断及鉴别、指导临床治疗、判断预后具有重要意义.     

100例慢性粒细胞白血病染色体核型分析

目的:分析慢性粒细胞白血病染色体核型的临床表现和特点。方法:选取我院2013年8月~2016年8月收治的100例慢性粒细胞白血病患者为主要研究对象,所有患者均接受骨髓或外周血细胞培养,采用G显带技术对100例患者的染色体情况进行检测,并对慢性粒细胞白血病患者的染色体核型进行回顾性分析。结果:100例慢性粒细胞白血病患者中,检出Ph(-)5例(5.0%);检出Ph(+)染色体共95例(95.0%),该染色体类型在慢性粒细胞白血病患者疾病发展的慢性期、疾病加速期以及疾病急变期均有出现。95例Ph(+)染色体患者中,Ph(+)细胞100%患者共84例(88.42%),Ph(+)细胞45%~96%患者共11例(11.58%)。结论:对慢性粒细胞白血病患者进行染色体核型分析,可了解患者病情的严重程度,同时可为疾病的早期诊断、治疗提供科学依据,判断预后。     

两例Ph阳性CML病人急变期前有3;21易位

慢性粒细胞白血病(CHL)患者除有Ph易位外,一少部分病例往往出现其它附加染色体畸变。慢性急变时异常染色体占病例的75%,一般包括双Ph、+8、+19、等臂17q染色体,也包括各种易位。最近,Rubin和他的同事在3例Ph阳性CML急变期病人中识别出一种新的异常核型-t(3;21)(q26;q22)。作者又报导两例t(3;21)(q26;22)出现在Ph阳性CML慢性期的病例。病例1:女性,黑人,18岁,1982年5月出现乏力,脾大。血象:血红蛋白9.7mg%,白细胞3.72×10~(11)/L,母细胞     

慢性粒细胞性白血病急变期的1号染色体畸变

发生于慢性粒细胞性白血病(CML)母细胞危象期(BC,即急变期)的染色体畸变并不少见,其最常见的类型为:8三体、i(17q)和/或Ph~1重复。大约 85％的CML患者,至少有上述一种改变。本文作者曾报告,在慢性期经强烈化疗的患者,约50％的病例有1号染色体的附加的结构改变。本文研究表明,CML患者的1号染色体仅仅某些部位选择性地受累,此类患者预后不良。材料和方法本文报告7例Ph~1阳性的CML患者,其1号染色体异常出现于急变期。这些患者选自本实验室1972年以来研究的一组50例Ph~1     

急性白血病、慢性髓细胞白血病及骨髓增生异常综合征患者染色体分析

目的探讨染色体分析在急性白血病（AL）、慢性髓细胞白血病（CML）及骨髓增生异常综合征（MDS）诊断及预后判断中的价值。方法采用骨髓细胞短期培养法,应用G、R显带技术对238例AL、CML及MDS患者进行染色体分析。结果56.30%的患者有染色体异常,其中数目异常占6.30%,结构异常占39.08%,复杂异常占10.92%;各组患者中CML组异常检出率最高,占总病例的34.87%;AL组染色体畸变最为复杂,累及除3,4,5,10及X以外的所有染色体,11例患者出现了特异性染色体畸变,与患者预后相关;CML加速/急变期出现了附加染色体异常;核型异常的MDS患者均检出了8三体,7例为单纯8三体,2例RAEB-T患者均为复杂异常。结论染色体检查对于疾病诊断与鉴别、指导临床治疗、判断预后等具有重要意义。     

慢性粒细胞白血病与Ag—NOR异型颗粒及骨髓染色体畸变相关研究

目的：研究银染核仁形成区异型颗粒和骨髓染色体畸变与慢性粒细胞白血病（CML）的相关性。方法：采用银染核仁形成区（Ag-NOR)染色技术和骨髓细胞短期培养制备染色体技术,分析60例不同病期的CML患者和20例正常对照组的Ag-NOR异型颗粒和染色体变异情况。结果：银染核仁形成区染色表明,病例组Ag-NOR染色计数颗粒总面积（GA）明显高于对照组（P＜0．05）;Ag-NOR染色计数颗粒总面积（GA）、Ag-NOR颗粒数（GN）,GA／细胞核面积（NA）的比率均随病情进展而增加。GN平均值急变期明显高于慢性期（P＜0．05）。骨髓染色体核型分析结果表明60例CML患者中58例有t(9:22)(q34;q11）易位,其中加速期、急变期患者还有其它变异。结论：CML与Ag-NOR异型颗粒及髓髓染色体变异具有相关性。     

成人Ph阳性急性淋巴细胞性白血病的分子异质性

Ph染色体最初认为是较短的第22号染色体,并在约90%的慢性粒细胞性白血病(CML)患者中发现。Ph染色体的t(9;22)将正常位于9号染色体的abl癌基因易位到22号染色体上,并与bcr基因融合,形成了新的bcr/abl融合基因,结果转录出新的8.5kb mRNA,由此翻译出具有210000分子量的融合蛋白质(P210)。在初次诊断为急性淋巴细胞性白血病 (ALL)的病人中,约5%的儿童和20～30%的成人也发现有Ph染色体。一些Ph(+)-ALL病人,可能在确诊前已处于未发现的CML慢性期。最近有二篇报道引起了作者的关注,一篇报道5例Ph(+)-ALL病人中的3例为bvr(-)。另一报道     

hPer3 基因启动子甲基化检测在慢性粒细胞白血病急变监测中的临床意义

目的: 探讨慢性粒细胞白血病(CML)急变中 hPer3 (human period 3)基因启动子甲基化检测的临床意义以及诱导 hPer3 表达对CML细胞株K562的作用。方法: 应用甲基化特异性PCR(MS-PCR)和实时荧光定量PCR检测29例CML患者骨髓 hPer3 基因启动子甲基化状态和mRNA表达,以40例缺铁性贫血(IDA)患者骨髓作为对照。将pcDNA3.1- hPer3 表达质粒经脂质体介导转染CML细胞株K562,MTT法检测生长抑制率,Annexin V/PI染色法检测细胞凋亡。结果: IDA组、CML慢性期、CML加速期和CML急变期中, hPer3 启动子甲基化阳性率(例)分别为0%(0/40)、17.65%(3/17)、66.67%(4/6)和83.33%(5/6),CML急变期和加速期甲基化阳性率均高于CML慢性期,差异显著(χ²=8.44,P＜0.01;χ²=5.03,P＜0.05)。对照组和CML慢性期、CML加速期和CML急变期中, hPer3 mRNA表达分别为75.03±18.16和5.13±2.29、0.40±0.18、0.17±0.05,两两之间差异显著(P＜0.01)。与空载体转染组相比, hPer3 转染后各时点的细胞抑制率和凋亡率均升高(P＜0.01)。结论: CML中 hPer3 启动子高甲基化导致了基因表达沉默,可能作为CML急变的监测指标。 hPer3 的过表达能抑制CML细胞株增殖,并促进其凋亡。     

细胞遗传学和分子遗传学揭示慢性粒细胞白血病进展过程中的染色体畸变:1q12-q21的意义

为了研究慢性粒细胞白血病 ( CML)急性转变中的基因异常 ,用常规细胞遗传学 ,比较基因组杂交( CGH) ,和双色染色体涂染的方法分析 1 5例急性危象期 ( BC)的 CML病人 ,和 3例进展期 ( AP)和 2 0例慢性期 ( CP)的 CML病人。在被研究的每一例中均发现 Ph染色体 ,2 0例 CP病人中仅有 5例有其他异常 ,而 1 8例疾病进展期 ( BC AP)病人中就有 1 3例表现其他数量和 /或结构上染色体畸变。细胞遗传学方面 ,在 BC和 AP期最常见获得的染色体为二个或三个 Ph染色体 ( 1 4例中 5例 ) ,和 8三体 ( 1 4例中 5例 )。也观察到 7和 1 7三体 ( 1 …     

Determination of secondary chromosomal aberrations of chronic myelocytic leukemia

Chronic myeloctyic leukemia (CML) is a stem cell disorder characterized by the cytogenetic abnormality of t(9;22)(q34;q11.2), which progresses from a chronic phase to an accelerated phase (AP), and/or a blast phase (BP) of myelocytic or lymphoid phenotype. This progression is frequently preceded or accompanied by recurring secondary chromosomal abnormalities (SCA) that are believed to play a role in the transformation and may also serve as valuable prognostic indicators. Failure to note such abnormalities may lead to an inappropriate clinical evaluation. We observed CML patients with AP or BP who did not show SCA by routine cytogenetic analysis. To determine the presence or absence of specific SCA in those cases, we applied fluorescence in situ hybridization (FISH) to four CML cases with pseudodiploid cytogenetics [t(9;22)(q34;11.2) as the sole abnormality] by conventional karyotyping. Bone marrow biopsies from two AP and two BP of CML patients with pseudodiploid karyotypes by conventional cytogenetics were examined by FISH for trisomy 8 and i(17q). These SCA are major secondary chromosomal changes seen in BP of CML patients. Results were considered positive if more than 2.4% of cells had +8 and >6.25% for i(17q) by FISH. Four out of four patients were positive for +8. These results indicate that FISH techniques are valuable in the determination of SCA in CML, which were t(9;22)(q34;q11.2) positive as the sole cytogenetic abnormality with standard G-banding karyotyping and can be helpful for the early diagnosis of CML progression.     

Emergence of unusual cytogenetic abnormalities under interferon-alpha therapy in patients with chronic myelogenous leukemia.

New treatments that may change the course of a disease or have potential carcinogenicity can result in the emergence of new cytogenetic or clinical disorders. We report here the cytogenetic evolution of 52 cases of Philadelphia (Ph)-positive myelogenous leukemia (CML) receiving interferon-alpha (IFN-alpha) therapy compared with that of 59 Ph-positive CML cases treated with busulfan (BU) or hydroxyurea (HY). Twenty-one percent of the CML patients receiving IFN-alpha displayed unusual secondary abnormalities, among which alteration of the long arm of chromosome 3, del(7), and del(9) were recurrent. The frequency of these unusual secondary changes was significantly higher than in CML cases after Bu or Hy treatment (P = 0.02). Three of the 11 IFN-alpha-treated CML patients displayed cytogenetic evolution in the chronic phase and, in two cases, the cytogenetic findings were transient, inasmuch as they disappeared upon withdrawal of IFN-alpha. In addition, a majority of cytogenetic abnormalities involved chromosome 3 at bands 3q21 and 3q26, which corresponds to the locus of EVI1, a gene implicated in the development or progression of human myeloid leukemias. Possible explanations include: toxicity of IFN-alpha by effect on bone marrow stroma, immune-modulating effects of IFN-alpha, and mutagenic effects of IFN-alpha. The mechanisms underlying these cytogenetic changes remain to be elucidated. However, our data suggest that IFN-alpha induces additional cytogenetic abnormalities even in the chronic phase through its immune-modulating effects and that these unusual cytogenetic abnormalities do not alter the history of CML.     

Risk factor analysis in myelodysplastic syndrome patients with del(20q): prognosis revisited

The deletion of the long arm of chromosome 20, or del(20q), is a common cytogenetic abnormality in various myeloid disorders and is known to be a favorable prognostic factor in myelodysplastic syndromes (MDS) when it is the sole change. However, del(20q) occurs with one or more cytogenetic changes when it is associated with disease progression. Here, we analyzed 33 patients with MDS and del(20q) to ascertain the risk factors in MDS. We categorized del(20q) into two groups: one with the del(20q) clone (> or =50% marrow metaphases), corresponding to genomic integrity, and the other with a late appearance of a minor del(20q) clone (<50% metaphases) with additional cytogenetic changes, representing genomic instability. Of the MDS patients with del(20q) at initial presentation, the negative factors in predicting prognosis on survival are (i) INT-2/High risk according to the International Prognostic Scoring System, (ii) any additional cytogenetic changes, or (iii) minor del(20q) clone. The late appearance of del(20q) at any phase is linked to a significantly unfavorable prognosis, thus indicating the clinical and biological heterogeneity of del(20q) in MDS.     

Cytogenetic follow-up after bone marrow transplantation for Philadelphia-positive chronic myeloid leukemia

Forty-eight consecutive patients affected by chronic myelogenous leukemia (CML) Philadelphia (Ph) chromosome positive during the chronic phase of the disease underwent allogeneic bone marrow transplantation (BMT). Thirty-five patients had a follow-up over 12 months and were included in a cytogenetic study in order to evaluate the Ph clone eradication. In 25 cases, the Ph chromosome disappeared in all cytogenetic studies, and their hematologic picture is at present apparently normal. Ten patients showed cytogenetic relapse. In one case, the cytogenetic relapse was transitory without any clinical sign of the disease; in three cases, after a transitory cytogenetic relapse, a persistent relapse with clinical picture of progression of the disease occurred; in six cases cytogenetic and a clinical relapse were coincident. Structural chromosomal abnormalities other than Ph were temporarily seen in three cases. The so-called "nonrandom" chromosomal changes typical of the blastic phase were never detected. The reappearing Ph-positive clone spontaneously disappeared in three patients, and their hematologic picture reverted to complete chimerism. The present study confirms that the eradication of the Ph clone is often defective with BMT, and cytogenetic analysis can detect the competition between donor and residual host marrow. Furthermore, the karyotype evolution is different from that found in CML patients treated with conventional chemotherapy.     

Karyotype evolution of Ph positive chronic myelogenous leukemia patients relapsed in advanced phases of the disease after allogeneic bone marrow transplantation.

Sixty-eight patients affected by Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) and were successfully studied from a cytogenetic point of view, before and after the BMT. Nineteen had evidence of cytogenetic and clinical relapse. Cytogenetic analyses of 14 patients who, after the relapse, showed progression to the accelerated or blastic phase of the disease, are presented. Five of these cases had only the Ph chromosome without karyotype evolution; in one case Ph duplication without other anomalies was detected, while in the remaining eight cases cytogenetic analysis showed apparently random clonal structural abnormalities (translocations, inversions, deletions, and marker formations). Therefore, the classical "non-random" abnormalities (+8, i(17q), +Ph, +19, +21) were not as common as in conventionally treated Ph+ CML. From our data, karyotype evolution during advanced phases in Ph+ CML patients after BMT differs from the evolution seen in conventionally treated patients, by the presence of numerous structural unusual abnormalities, possibly related to radiochemotherapy conditioning to BMT. Therefore, BMT treatment is not always able to eradicate the Ph+ clone but can reduce the incidence of the formation and/or expansion of Ph+ clones with additional non-random abnormalities.     

Clinical features of a new category, myelodysplastic/myeloproliferative diseases, defined by WHO classification

The WHO classification published in 2001 defined a new category of hematological disease, myelodysplastic/myeloproliferative diseases (MDS/MPD), that have both myelodysplasia and myeloproliferation at the time of initial presentation. This category consists of four subclasses, chronic myelomonocytic leukemia (CMML), atypical CML(aCML), juvenile chronic myelogenous leukemia and MDS/MPD-unclassifiable (MDS/MPD-u). In order to clarify the clinical features of these diseases, we analyzed clinical data of tentatively diagnosed MDS/MPD cases in the past ten years accumulated from affiliated hospitals. By reviewing the data of each case according to the criteria, we diagnosed 31 cases of MDS/MPD, including 22 cases of CMML, 5 cases of aCML and 4 cases of MDS/MPD-u. Male predominance and high age were common among these three subclasses. The prognosis of CMML was poor compared to other subclasses because of the high incidence of blast crisis. It is noteworthy that blast crisis in CMML exclusively occurred within one year after diagnosis. Young age, a high percentage of blasts in the peripheral blood, splenomegaly, lymphadenopathy and clonal cytogenetic abnormality were associated with blast crisis. It is suggested that there are two subgroups in CMML which differ in disease progression. Thus, these indicators may be useful in deciding the therapeutic strategy including hematopoietic cell transplantation for the high risk subgroup. There were four MDS/MPD cases with a history of preceding hematological diseases, such as aplastic anemia, MDS or malignant lymphoma. Among these, three cases with a long-term history of treatment with metenolone acetate developed CMML. It is suggested that the long-term effect of androgen plays a role in the pathophysiology of CMML.     

Cytogenetic follow-up of patients with nonlymphocytic leukemia I. Philadelphia chromosome-positive chronic myeloid leukemia

Chromosomes of blood and bone marrow cells were studied in 53 patients with Philadelphia chromosome (Ph¹)-positive chronic myeloid leukemia (CML). Fifty patients presented with t(9;22) and three with variant translocations: t(17p+;22q?); t(17q+;22q?), and t(1;9;22). Serial studies were carried out in 27 patients during both the chronic and the blastic phase of the disease. Five patients in the chronic phase developed cytogenetic changes in addition to the Ph¹. In two of these cases the changes preceded a transformation into acute leukemia, but in three cases no acceleration of the disease has occurred 1 to 4 years after the emergence of the subclones. Blastic transformation occurred in 15 instances; 11 of these patients acquired additional nonrandom chromosomal changes: trisomy 8 (9 times), i(17q) (4 times), trisomy 17 (2 times), trisomy 19 (7 times), and duplication of the 22q? (6 times). Clonal evolution was found in eight cases, either at the onset of blastic transformation or later in follow-up cultures. The differences between karyotypic evolution during the chronic and blastic phases of CML are discussed, together with their prognostic significance.     

A case of myeloid sarcoma diagnosed by FISH

Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site or in bone. The tumor mass may precede or occur concurrently with acute or chronic myeloid leukemia or with other types of myeloproliferative disorders or myelodysplastic syndromes. MS is a rare disease, estimated to comprise between 2 to approximately 14% of acute myeloid leukemia. On the other hand, 95% of cases of CML have characteristic t (9;22) cytogenetic abnormality and BCR/ABL fusion gene at diagnosis. We here report the clinical significance of FISH in a diagnosis of MS that formed tumor in femur during the chronic phase of CML.