间期荧光原位杂交对骨髓增生异常综合征患者5号和7号染色体异常的检测

目的筛选经济、实用的探针组合提高MDS染色体异常的检出率；比较常规细胞遗传学分析（CCA）及荧光原位杂交（FISH）两种技术在MDS染色体异常检测中的灵敏度和特异性。方法采用CCA法和HSH法分析48例患者骨髓细胞的染色体异常情况。结果CCA检出染色体异常18例（37．5％），其中复杂异常4例（8．3％），＋8异常8例（16．6％）、-5／5q-异常5例（10.4％），-7／7q-异常5例（10.4％）、20q-异常2例（4．6％）、不一致的易位3例（6．2％）。FISH除证实CCA发现的-5／5q-和-7／7q-各5例外，还检出2例有5q-，5例有7q-，1例有-7，从而使-5／5q-和-7／7q-的检出率分别增至14．5％和22．9％。平均随访12个月，38例存活，10例死亡，5例转变为急性白血病。结论CCA结合FISH能提高MDS染色体异常的检出率，与CCA相比，采用组合探针的HSH更为敏感和特异。     

荧光原位杂交技术在骨髓增生异常综合征患者5号和7号染色体异常检测中的应用

目的评价荧光原位杂交（FISH）术在骨髓增生异常综合征（MDS）患者5号和7号染色体异常检测中的应用。方法 40例MDS患者,采用间期FISH,选取4种探针组合检测-5/5q-和-7/7q-。结果利用FISH技术,5号、7号染色体异常检出率分别为15.0%、20.0%。结论 FISH技术可以用于骨髓增生异常综合征（MDS）患者5号和7号染色体异常的检测,采用组合探针的FISH更为敏感和特异。     

恶性髓系血液病-7/7q-异常的分子细胞遗传学分析

目的 分析染色体-7／7q-在骨髓增生异常综合征(myelodysplastic syndrome，MDS)和急性髓细胞白血病(acute myeloblastic leukemia，AMI，)中的发生频率；探讨荧光原位杂交技术(fluorescence in situ hybridization，FISH)在检测和鉴定-7／7q-异常中的价值。方法 回顾性分析所有接受细胞遗传学分析(conventional cytogenetic analysis，CCA)的MDS／AML患者的核型特征，其中70份进行FISH分析。应用双色荧光直接标记的7号着丝粒探针(CEP7，光谱绿)和7q31基因序列探针(D7S486，光谱桔红)，15份正常样本作为对照。结果 -7／7q-在AML和MDS中出现频率分别为4．5l％(31／687例)和5．7l％(28／490例)，分别占异常核型病例的5．68％和l0．29％。7q-常见的缺失区域为7q21—22(10例)和7q31—35(10例)。FISH证实伴有克隆性-7／7q-异常，但在随机性-7／7q-异常或正常核型中未检出-7／7q-异常。在核型分析出现7q-异常的病例中，FISH检出7／11例可同时伴有-7克隆的出现，而且7q-异常的细胞数显著高于-7异常细胞数(42．5％vs8．4％，P=0．025)。1例核型为del(7)(q22)患者FISH证实为染色体易位；1例7q 患者FISH显示dup(7q)；1例复杂异常核型，FISH确定其累及7q。结论 FISH是鉴定或确定7q结构异常的强有力工具，能精确地评价-7／7q-。7q-异常通常与-7异常在同一个样本中共存，且7q-细胞数显著增高，推测-7克隆衍生于7q-的丢失。     

骨髓增生异常综合征的临床与细胞遗传学研究

目的研究骨髓增生异常综合征（myelodysplastic syndrome，MDS）的细胞遗传学、血液学与预后的相互关系。方法采用骨髓直接法和24小时短期培养法制备染色体标本，用R显带技术，对50例MDS进行核型分析。结果50例MDS中，发现有异常核型22例，发生率44．0％（22／50）。异常类型6种：2例add（8）；4例-7；4例5q-；9例7q-；2例20q-；1例6q-。结论5q-，-7，7q-是MDS中最为常见的染色体核型异常，伴有5q-染色体核型异常的预后较好，而伴有-7，7q-核型异常的预后不良。细胞遗传学在MDS的诊断、病情发展和预后判断中有着至关重要的作用。     

应用组合荧光原位杂交技术检测慢性淋巴细胞白血病的基因组异常

目的 探讨应用组合荧光原位杂交(panel fluorescence in situ hybridization，panel FISH)技术对慢性淋巴细胞性白血病(chronic lymphocytic leukaemia，CLL)基因组异常检测的价值。方法 分别应用3号、12号、18号的着丝粒探针和序列探针D13S272(13q14．3)、ATM(11q23)等5种荧光素标记的DNA探针，对22例CLL患者进行FISH检测，并和常规细胞遗传学检测结果进行比较，以确定何种方法对检测CLL的染色体和基因组异常更为敏感可靠。结果 22例CLL患者中，常规细胞遗传学检测出8例(36．3％)有染色体异常，包括单纯 123例； 3、 12l例； 3、 12、 18 1例；t(5；15)1例；13q-1例；3q-、18p 1例；4q 和13q-1例；组合FISH检测出15例(68，1％)有染色体异常，包括 34例、 126例、 18l例、11q-6例、13q-8例。结论组合。FISH技术是检测CLL患者染色体基因组异常的有效手段，与常规细胞遗传学方法相结合则可明显提高CLL染色体异常的检出率。     

八探针荧光原位杂交联合R显带技术诊断儿童急性髓系白血病CSCD

目的探讨将八探针荧光原位杂交（fluorescence in situ hybridization, FISH）联合R显带染色体核型分析应用于儿童急性髓系细胞白血病（acute mydoid leukemia,AML）诊断的价值。方法应用八探针FISH（AML1／ETO、PML—RARa、CBFβ／MYH11、mL、P53、5q-、7／7q-、20q-等8种DNA探针）和R显带染色体核型分析技术,对214例AML患儿进行了联合检测。结果八探针FISH技术在118例患儿中检出了细胞遗传学改变,总体阳性率为55．1％,包括AML1／ETO、PML／RARa、CBFβ／MYH11、MLL、P53、5q-、7／7q-、20q-等8种细胞遗传学异常。R显带核型分析检出染色体异常55例,阳性率为25．7％,其中4例染色体异常FISH未检出。两种方法检出阳性率的差异有统计学意义（P〈0．05）。结论八探针FISH技术较R显带染色体核型分析具有准确、高效、省时、省力等优点,可与染色体核型分析有效互补,并且每种细胞遗传学异常都可为儿童AML的诊断、预后评估和个体化治疗提供重要依据。     

多探针荧光原位杂交检测急性髓系白血病常见细胞遗传学异常

目的:评价多探针荧光原位杂交(FISH)在检测急性髓系白血病(AML)常见细胞遗传学异常中的价值,探讨细胞遗传学异常与临床诊断、治疗、预后的关系。方法:采用针对AML/MDS的FISH多探针诊断系统,即以针对AML1/ETO融合基因、PML-RARα融合基因、CBFβ/MYH11融合基因、MLL基因、P53基因、Del(5q)、Del(7q)、Del(20q)8种DNA探针对40例患者进行多探针FISH检测,同时联合染色体核型、临床资料进行研究。结果:40例AML中,共22例多探针FISH检出了细胞遗传学改变,包括:AML1/ETO、PML-RARα、MLL基因断裂重排、Del(5q)、Del(7q)、P53基因缺失、8号染色体三体7种细胞遗传学异常。而常规染色体核型分析仅检出11例遗传学异常。多探针FISH与染色体核型分析的总阳性率分别为57.50%及27.50%。AML1/ETO、PML/RARα阳性者首次诱导化疗效果较理想;而Del(7q)、MLL基因断裂重排阳性、伴复杂细胞遗传学改变者可能预示不良预后。结论:FISH多探针诊断系统检测AML患者常见遗传学异常更省时、准确、高效,有利于完善白血病的分层诊断及指导临床个体化治疗。     

骨髓增生异常综合征细胞遗传学研究进展

骨髓增生异常综合征（MDS）为一类获得性干／祖细胞疾病,易发展为急性白血病,MDS常有细胞遗传学异常,且染色体异常与MDS的疗效及预后关系密切。近年来的研究主要包括：5q-综合征重要缺失区域;7q-、-7染色体异常的多发重要部位;inv(16）和罕见CBFB,MYH11基因重排的发生频率和相关因素;11q23异常及DNA拓扑异构酶Ⅱ抑制剂早期化疗与某些染色体畸变的关系等。     

荧光原位杂交技术对骨髓增生异常综合征患者染色体异常的检测分析

目的:分析荧光原位杂交(FISH)技术对骨髓增生异常综合征(MDS)5、7、8、20号染色体异常检出率,并与常规细胞遗传学分析(CCA)进行比较。方法:收集48例MDS患者骨髓标本,CCA采用骨髓短期培养法及G带核型分析。FISH采用间期FISH,选取针对5、7、8、20号染色体的不同探针组合。χ2检验比较两种方法检出率。结果:CCA对5、7、8、20号染色体异常检出率分别为8.33%、12.50%、6.25%、12.51%,总的异常检出率为39.58%;FISH对5、7、8、20号染色体异常检出率分别为12.50%、16.67%、10.42%、16.67%,总的异常检出率为56.25%。两法检出率差异无统计学意义(P>0.05),但FISH检测时间(2～3天)明显短于CCA(10～14天)。结论:FISH检测MDS患者5、7、8、20号染色体异常是CCA的重要补充,并明显缩短检测时间。     

应用荧光原位杂交技术验证骨髓增生异常综合征的非克隆性染色体异常

目的探讨应用荧光原位杂交(FISH)技术验证骨髓增生异常综合征(MDS)经传统染色体显带分析(CBA)检测到的非克隆性染色体异常(n-CCA)的价值。方法回顾性分析2011年10月至2020年12月北京大学人民医院CBA检测具有n-CCA的91例MDS患者的临床资料及染色体核型和FISH检测结果。结果在91例患者中, CBA共检测到94例次非克隆性+8、5q-、-7、7q-和20q-异常, 其中43例次(45.7%)经FISH验证为阳性, +8、5q-、-7、7q-和20q-的验证率分别为47.6%(30/63)、25%(2/8)、41.7%(5/12)、40%(2/5)和66.7%(4/6), FISH阳性的细胞占比为4% ～ 90%(中位7%)。将91例患者按CBA分析的中期分裂相数目分为3组, 即≥ 20、10 ～ <20、< 10。3组的FISH验证率分别为43.7%(31/71)、33.3%(3/9)、63.6%(7/11), 未见明显差异(P>0.05)。对26例仅接受支持治疗的患者进行连续监测, 结果显示91.7%(11/12)经FISH验证的异常持续存...     

骨髓增生异常综合征的-7/7q-染色体异常的检测

目的　探讨间期荧光原位杂交(fluorescence in situ hybridization,FISH)技术在检测骨髓增生异常综合征(myelodysplastic syndrome,MDS)-7/7q-染色体异常中的价值。方法　同时应用常规细胞遗传学(conventional     

Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia

Complex chromosomal aberrations are present in < or =30% of patients with primary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and are associated with a poor prognosis. Specific alterations in complex karyotypes are difficult to define by conventional cytogenetics alone. To obtain a more comprehensive view of the recurrent aberrations, we performed spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) with selected probes on bone marrow samples from 17 patients with primary MDS and 3 with primary AML. All cases had chromosome 5 alterations. Two different types of 5q loss were identified: unbalanced translocations and interstitial deletions, or del(5q), each occurring in 10 patients. The most frequent additional chromosome aberrations were -3/-3p/-3q, -7/7q-, +8, 13q-, -16, 17p-, -18/18p-, -20/20q-, and +21q, each occurring in 25%. In the five cases with gain of 21q, involvement of the AML1 gene was excluded. Unbalanced 5q translocations occurred more often in combination with monosomy 3 and 7 and with gain of 21q, whereas del(5q) was associated more often with -1p and trisomy 8. A detailed analysis of specific breakpoints and deletions revealed recurrent involvement of specific chromosomal bands harboring known tumor suppressor genes or oncogenes. Analysis of large numbers of MDS and AML cases in a similar detailed manner with SKY and FISH will reveal whether new subgroups can be identified according to their genetic alterations. Correlation with clinical parameters may reveal the prognostic significance of these genetic subgroups.     

Predominance of trisomy 1q in myelodysplastic syndromes in Korea: is there an ethnic difference? A 3-year multi-center study

A predominance of total or partial chromosomal losses and the rarity of translocations are characteristics of myelodysplastic syndrome (MDS), and 5q,-5, -7 and +8 are known to be the most predominant chromosomal changes. To investigate whether the incidence and the pattern of chromosomal changes in MDS varies by location in Korea, we reviewed the cytogenetic results of 205 MDS cases from three medical centers. Distribution of MDS subtypes and the incidence of chromosomal aberration (44.8%) of MDS in Korea were similar to those found in other countries, however, their patterns were different. Translocations (40.4%) predominated over partial or total deletions (36.3%) in Korea. The most common abnormalities in MDS were trisomy 8, trisomy 1q, -5/5q-, and -7/7q-, which occurred in 18(19.5%), 14(15.2%), 12(13.0%), and 11(11.9%) patients, respectively. It is of note that trisomy 1q, which is rarely reported in hematologic malignancies, was the second most common change associated with MDS in Korea, and that structural anomalies of chromosomes 1(19.6%) exceeded that of chromosome 5(15.2%). The most common sole anomalies were trisomy 8(7.6%) and 14(78%) of 18 cases with chromosome 1 anomalies accompanied by other chromosomal abnormalities, suggesting that the changes of chromosome 1 may be evolutionary events rather than sporadic events. In conclusion, trisomy 1q and trisomy 8 predominate in Korean MDS, suggesting the likelihood of ethnic differences.     

Cytogenetic analysis of hematologic malignancies in Hong Kong. A study of 98 cases.

The karyotypes of 98 patients between the ages of 8 and 81 years with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloid leukemia (CML) are presented. Although the well-described cytogenetic abnormalities associated with particular FAB subtypes in the West were observed, certain important local differences were noted. In ALL, hyperdiploidy was rarely observed, whereas the Philadelphia chromosome was observed in 50% of abnormal karyotypes. In AML, the t(8;21) was infrequently observed in M2 case, whereas trisomy 4 and 6, rarely reported elsewhere, formed 12% of the abnormal cases. In MDS, the incidence of -5/5q- and/or -7/7q- was 83% of cases with aberrant cytogenetic findings. Neither i(17q) nor an extra Ph was seen in 26 cases of CML including 9 cases of accelerated phase/blast crisis. In addition, previously unreported cytogenetic abnormalities occurring as single cases are presented. These findings are discussed in the context of geographical heterogeneity of chromosomal abnormalities in leukemia and emphasize the importance of continued epidemiologic studies of cytogenetics in hematologic malignancies.     

Fluorescence in situ hybridization for the study of cell lineage involvement in myelodysplastic syndromes with chromosome 5 anomalies

Fluorescence in situ hybridization (FISH) with a locus-specific dual DNA probe (LSI EGR-1SO/D5S23SG) for chromosome 5 was used in combination with morphology to study bone marrow cell lineage involvement of the abnormal chromosomal clone in 13 patients with deletion 5q [del(5q)], either as a sole aberration or as part of a complex karyotype, and in six cases with monosomy 5 by metaphase cytogenetics, all with complex karyotypes including 2-6 marker chromosomes. In the monosomy 5 group, only one case displayed the expected one orange and one green (1O + 1G) FISH pattern in a majority of the cells. The other five patients instead showed 1O + 2G FISH signals in 17-86% of the bone marrow cells, which is the typical pattern for del(5q). In the del(5q) group, 26-98% of the bone marrow cells exhibited 1O + 2G FISH signals. All patients showed clonal involvement of the myeloid cell lineages, including the megakaryocytes in a few cases, whereas lymphoid cells generally exhibited the normal 2O + 2G FISH pattern. No difference was seen between patients with 5q- syndrome, those with del(5q) and a complex karyotype, and the monosomy 5 group. We were thus unable to confirm the recent suggestion that B-cells are a part of the abnormal clone in MDS with del(5q). Furthermore, true monosomy 5 seems to be rare in MDS.     

Diagnostic yield of bone marrow and peripheral blood FISH panel testing in clinically suspected myelodysplastic syndromes and/or acute myeloid leukemia: a prospective analysis of 433 cases

It is unclear how often and in what setting fluorescence in situ hybridization (FISH) panels for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) provide additional information over metaphase cytogenetics alone. Furthermore, the usefulness of peripheral blood vs bone marrow FISH has also not been directly compared. We prospectively compared metaphase cytogenetics and FISH for -5/5q-, -7/7q-, +8, and 20q- in 433 cases of suspected MDS/AML. FISH testing was abnormal in 6 (14%) of 43 and 10 (19%) of 54 cases with fewer than 20 normal metaphases or no growth, respectively. FISH was only rarely abnormal in cases with 20 normal metaphases obtained (6/222 [2.7%]). Comparison of peripheral blood and bone marrow results in 48 cases showed abnormal peripheral blood FISH results in 18 (69%) of 26 cases with abnormal bone marrow FISH results and in 5 (23%) of 22 cases with normal bone marrow FISH results. These findings, the largest published comparison of FISH vs metaphase cytogenetics in MDS/AML, provide a rational strategy for FISH testing in peripheral blood and bone marrow.