一例急性早幼粒细胞白血病同时伴有ins(15;17),t(2;17;20)和三体8异常

目的 对1例伴有ins(15;17),t(2;17;20),+8复杂异常的急性早幼粒细胞白血病(acute promyelocytie leukemia,APE)病例进行细胞和分子遗传学研究.方法 按常规制备染色体,以R显带技术进行核型分析,并先后作多色荧光原位杂交(multiplex fluoresence in situ hybridization,M-FISH)、染色体涂染和PML-RARa双色FISH检测.结果 R显带核型分析为47,XY,2q-,+8,17q+,20p+;M-FISH检测为:47,XY,t(2;17;20)(q24;q21;p13),+8;染色体涂染证实了2qZ4以下片段易位到17q21上和17q21以下片段易位到20p13上;双色FISH示17号染色体上RARa(retinoic acid receptora,RARe)基因部分片段插入到15号染色体形成PNL-RARa融合基因,即ins(15;17)(q22;q21.1q21.3).结论 FISH技术是明确隐匿/插入易位的可靠手段,凡形态学拟诊为APL而常规核型分析未发现t(15;17)者均应进行FISH检测.     

135例慢性粒细胞性白血病细胞遗传学分析

目的探讨慢性粒细胞性白血病(CML)的细胞遗传学特点及意义.方法采用24h短期培养法制备骨髓染色体.G显带技术进行染色体核型分析并照相.结果本研究135例患者中有108例Ph( )(占80%),27例ph(-)(占20%);108例Ph( )病例中,具有典型易位即t(9;22)(q34.1;q11.21)100例,变异易位和涉及其他染色体异常的有8例.47,XX, 8,t(9;22)/46,XY 1例;49,XY 8、 9、 20,双Ph( )1例;46,XX,t(9;22)-17 i(17q)1例(慢粒急变).2例单纯变异Ph易位t(17;22)和t(21;22),3例复杂变异易位为46,XX,t(5;9;22)和46,XX,t(7;9;22),46,XX,t(9;12;22).结论白血病进行细胞遗传学研究对疾病的诊断和预后判断具有重要的价值.     

急性早幼粒细胞白血病(APL)的染色体异常

作者在5年间诊断了29名APL患者,其中18名(62％)作了细胞遗传学检查,16名(55％)成功。16名APL患者(一名儿童)中,14名有异常的核型(87％),其中11名有t(15;17)(q26;q22)的结构异常,一名核型为47, 8,一名是与其他患者有明显不同的染色体15和17的重组,一名有染色体17的缺失,却没有易位的证据。作为另一种染色体变化,5名患者有三体8,     

t(15;17)的变异型插入易位ins(17;15)(q21;q14q22)的细胞遗传学和分子遗传学研究

目的　报道 1例 t(15 ;17)的变异型插入易位 ins(17;15 ) (q2 1;q14 q2 2 )病例及其染色体涂染、逆转录 - PCR的研究结果。方法　骨髓细胞经直接法或 2 4 h培养和外周血单采白血病细胞培养 6天后制备染色体标本 ,以 R显带技术进行核型分析 ;以 15号和 17号整条染色体涂染探针进行染色体涂染 ;以逆转录 -PCR技术检测 PML - RARα和 RARα- PML融合基因的转录本。结果　该患者骨髓细胞和外周血白血病细胞染色体 R显带核型分析结果均提示 15 q-和 17q ;涂染研究证实 17号染色体长臂插入一段 15号染色体来源的染色体片段 ;逆转录 - PCR检出 PML- RARα融合基因短型转录本 ,未检出 RARα- PML 融合基因的转录本 ,符合 ins(17;15 )所致的遗传学改变。结论　染色体涂染和逆转录 - PCR技术是明确急性早幼粒细胞白血病患者涉及 15和 17号染色体插入易位的可靠手段。     

急性淋巴细胞白血病的t(1;19)(q21;q13)易位

在Kaneko等(1982年)报道的许多急性淋巴细胞白血病(ALL)的患者中,一例非B,非T ALL的3岁女孩,在诊断和复发时都发现有相互易位的改变,t(1;19)(q21;q13)。在第三届白血病染色体专业会议的330例ALL患者中,她是唯一具有此种易位的病例。作者发现一例患有非B,非T高危ALL的22个月的男孩,也具有同样易位。诊断时,其核型为46,XY/47,XY,-F, 2C;复发时,核型为47,XY, 8,-19, t(1;(19)(q21;q13);inv(5)(q13q35)。该病例的t(1;19)易位,系第一号染色体部分三体所致。     

慢性粒细胞白血病急变期的分子特征

慢性粒细胞白血病(CML)是一种粒细胞增殖性疾患,临床可分三期。起始期的细胞遗传学特征为,具有9q34与22q13相互易位形成的Ph染色体。c-abl和bcr基因分别位于9号和22号染色体长臂的断裂点附近。基本上具有t(9;22)的CML患者都存在这两个基因的相互易位。当CML发展至急变期(CML-BP)时,就出现另一些细胞遗传学畸变。其中最为常见的是Ph染色体复制和     

急性早幼粒细胞性白血病染色体的畸变

1980年第二次国际白血病染色体讨论会,综述了80例急性早幼粒细胞性白血病(APL)资料,发现异常染色体核型占40例,其中的33例带有一个典型易位染色体:t(15;17),其余40例属正常核型。Teerenhori等在1978年第一次国际白血病染色体讨论会上报告:t(15;17)的出现有地理     

慢性粒细胞白血病的一种少见的染色体演化——Y染色体重复

Y染色体重复是慢性粒细胞白血病(CML)一种罕见的染色体演化,关于出现此种非整倍体的意义,目前尚未见有探讨。本文报导两例CML急变期骨髓细胞发现Y染色体重复的研究,作者结合文献资料进行比较,并提出了初步的看法。两例CML均为老年男性,一例62岁,慢性期核型为46,XY,t(9;22)(q34;q11),急变期核型演变为48,XYY,+21,t(9;22)(q34;q11)。另一例56岁,慢性期核型为46,XY,t(9;22)(q34;q11),急变时除出现Y染色体增加外还伴有其它染色体的重复(8和Ph~1)、易位[t(6;8)(q34;q11)]和17号等臂染色体[i(17q)]。     

急性早幼粒细胞白血病细胞分化的调控机制新进展

急性早幼粒细胞白血病(APL)在1957年首次被描述为急性髓系白血病的一个常见亚型,占急性髓系白血病的10%～15%,以t(12; 17)(q22; q12)易位为特征,主要表现为未成熟的粒细胞在发育早期分化阻滞。而影响APL细胞分化的因素有很多,包括基因表达异常、自噬、氧化应激、表观遗传学等。目前,通过促进APL细胞分化的治疗可降低死亡率,延长持续缓解时间。本文主要对调控APL细胞分化的因素及其机制进行综述。     

伴复杂核型异常的髓系恶性血液病中17号染色体异常分析

目的 研究伴复杂核型异常(complex chromosomal abnormalities,CCAs)的髓系恶性血液病中17号染色体的异常特征.方法 经R显带常规细胞遗传学分析显示CCAs的73例髓系恶性血液病,包括21例急性髓系白血病(acute myeloid leukemia,AML)、36例慢性髓系白血病(chronic myeloid leukemia,CML)、16例骨髓增生异常综合征(myelodysplastic syndrome,MDS),并进一步多重荧光原位杂交分析.结果 73例伴CCAs的髓系恶性血液病中,17号染色体异常最常见,占46.5%(34/73),其中AML12例,CML13例,MDS9例,9例CML慢性期患者均未见17号染色体异常.结构异常较多见,总发生率为43.8%(32/73);AML、CML、MDS3组发生率分别为52.4%(11/21)、33.3%(12/36)、56.3%(9/16);所有病例中发生数目异常共15.1%(11/73),三组发生率分别为25.0%(3/12)、38.5%(5/13)、33.3%(3/9),11例数目异常均为-17.有9例同时出现数目异常和结构异常.伴有17号染色体的结构异常中,以非平衡易位多见,3组分别为16、15、8个;平衡易位2个,分别为发生于AML中的t(15;17)及发生于CML中的t(15;17;22).17号染色体结构易位的对手染色体多变,包括了除5号、6号和22号外的所有染色体.结构易位频率最高的对手染色体是15号,占8.2%(6/73);其次为2号,占5.4%(4/73).6例存在17号与15号易位的病例中5例为急性早幼粒白血病,1例为CML急变期.结论 伴CCAs的髓系恶性血液病中17号染色体异常发生率高,以结构异常为主.所有的数目异常均为-17;结构异常以非平衡易位多见.     

Cytogenetic findings in patients with acute promyelocytic leukemia and a case of CML blast crisis with promyelocytic proliferation

Nineteen patients with acute promyelocytic leukemia (APL) and one with promyelocytic blast crisis were studied by a methotrexate cell synchronization technique and by 24-hour short-term culture. Nineteen cases of APL included two cases of the microgranular variant (M3V). Except in one case of M3V, t(15;17) was detected in all patients. The breakpoints were determined as 15q22 and 17q12-21. A chronic myeloid leukemia (CML) blast crisis patient with high promyelocyte count also had a t(15;17) as well as a masked Ph chromosome. Other abnormalities, such as +8,del(7q) and an i(17q), were also observed in some patients. Our studies have indicated that 1) the translocation (15;17), characteristic of APL, was present in our population in almost all patients; 2) the presence of an identical abnormality in a promyelocytic CML blast crisis supported and confirmed the phenomenon of association of specific chromosome change with target cell type; and 3) the precise localization of breakpoints on chromosome 17 is still difficult to determine. The identification of as yet unknown genes at region 17q11-q21 and their subsequent translocation on chromosome 15 will help in assigning a precise position to these breakpoints.     

Trisomy 21 and other chromosomal abnormalities in acute promyelocytic leukemia

We describe a case of acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) and trisomy 21 as an additional change in a patient who died at relapse after achieving complete remission (CR) for the duration of 20 months. A survey of 42 cases of APL with cytogenetic study performed at our institution over the past 10 years showed 12 cases (28.6%) having chromosomal changes in addition to t(15;17). Trisomy 8 and trisomy 21 as additional changes were noted in 4 and 2 cases, respectively, with one patient showing both trisomies simultaneously. Two cases showed t(15;17) in hyperdiploid clones. Among the 10 patients with follow-up data, all eventually relapsed and none achieved continuous complete remission 1. Survival analysis performed in APL patients with adequate follow-up data showed no significant difference in overall and disease free survival between those with and without additional cytogenetic changes. After excluding cases with one induction death, the overall survival was significantly in favor of the group without additional cytogenetic abnormalities (P = 0.022). Late relapses may therefore be significantly more common in APL patients with additional cytogenetic abnormalities, and may not be reflected by analysis focused at three-year survival only. As APL is now considered a curable disease, any confirmed long-term survival impact of additional cytogenetic changes is expected to have important management implications.     

The nature and mechanisms of chromosome banding

Cytogenetic, morphologic, and clinical data of 33 acute nonlymphocytic leukemia (ANLL) patients with t(8q?;21q+) and 19 patients with acute promyelocytic leukemia (APL) were collected from seven laboratories in Japan. The latter class included 18 patients with t(15q+;17q?) and one with a normal karyotype. The t(8q?;21q+) and t(15q+;17q?) translocations were each shown to be associated with a specific type of ANLL, namely, AML-M2 and APL-M3, respectively. No patient with APL had the M3 variant. The t(8q?;21q+) translocation seems to be more common as an abnormalitu in ANLL in Japan as compared to findings in other countries. The high incidence of t(15q+;17q?) among Japanese patients with APL indicated in this study, however, still awaits confirmation.     

15;17 translocation in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a relatively rare subtype of leukemia that has been reported to be associated with a specific chromosome abnormality, t(15;17). It has been suggested that this translocation may have a geographical distribution and its presence may signify a poorer prognosis. In this present series of 14 patients with APL, 9 patients (64%) had the t(15;17) and 5 did not; however, no significant differences in clinical features or outcome could be found between those who did and those who did not express the translocation. When ethnic backgrounds were explored, no differences were found. More cases of the t(15;17) were found in recent years (7 of 8 patients studied since 1978 compared to 2 of 6 before 1978). This corresponded to changes made in our cytogenetic techniques suggesting that the finding of the t(15;17) may be a function of technique, rather than a real difference in disease entities, and all patients with APL may have the t(15;17) when appropriately studied.     

A variant t(X;15)(p11;q22) translocation in acute promyelocytic leukemia

Nonrandom reciprocal translocations involving chromosomes #15 and #17 are characteristic anomalies in a great majority of cases of acute promyelocytic leukemia (APL). Other complex translocations in APL that invariably involve chromosome #17 also have been described. We describe a patient with clinical and morphologic characteristics of APL but with a previously undescribed acquired karyotype, t(X;15)(p11;q22). This is the first translocation in APL described in which chromosome #17 is not involved. Although a comparative structure/function analysis of potentially relevant genes to the translocation breakpoints in both t(X;15) and t(15;17) APL showed no major alterations, the enhanced expression of the c-Ki-ras oncogene observed in t(X;15) APL supports the concept of heterogeneity in APL at the cytogenetic and molecular levels.     

Chronic myelomonocytic leukemia with trisomy 8 and a related clone with trisomy 8 and t(15;17)

We describe a patient with chronic myelomonocytic leukemia who showed trisomy 8 in 100% of his bone marrow metaphases. Of interest was the finding that 20% of the Giemsa-banded metaphases also showed t(15;17)(q22;q21), with breakpoints indistinguishable from those seen in cases of acute progranulocytic leukemia (APL). The patient showed no morphologic or clinical evidence of APL, and he died after 6 months, with no evidence that the disease had progressed to acute leukemia. Although cytogenetically the breakpoints appeared to be the same as those in APL, we suspect that this patient's translocation may have differed at the molecular level from the t(15;17) commonly seen in APL.     

Breakpoint clusters of the PML gene in acute promyelocytic leukemia: Primary structure of the reciprocal products of the PML-RARA gene in a patient with t(15;17)

DNA studies of the translocation t(15;17) in acute promyelocytic leukemia (APL) have shown that the retinoic acid receptor alpha (RARA) gene on chromosome 17 is juxtaposed to the promyelocytic leukemia (PML) gene on chromosome 15. The PML breakpoints have been mapped to 3 clusters: bcr1, bcr2, and bcr3. We have examined the PML breakpoint distribution in a series of 33 Chinese patients with APL Twenty-two patients fell within bcr1, 2 within bcr2, and 9 within bcr3. The primary structure of the reciprocal chromosome translocation joints of one patient and that of their normal counterparts have been determined and compared to those of 2 previously reported cases. These studies revealed possible topoisomerase II cleavage sites close to the breakpoints and suggested implications of DNA attachment sites to nuclear matrix. We propose that these features are relevant to the process of illegitimate recombination generating the translocation. © 1993 Wiley-Liss, Inc.     

Complex variant 15;17 translocations in acute promyelocytic leukemia. A case report and review of three-way translocations.

Complex variant 15;17 translocations are increasingly recognized in acute promyelocytic leukemia (APL). We report a novel three-way translocation in APL involving chromosomes 15, 17, and X in the form of t(X;17;15)(q13;q12;q21). Southern blot analysis showed retinoic acid receptor alpha (RARA) gene rearrangement at intron 2. Clinical and morphologic findings are typical of APL, and a complete remission was attained with a course of conventional chemotherapy. A review of three-way complex variants of 15;17 translocation in the literature reveals 21 published cases in addition to ours. PML/RARA fusion was observed in all 8 cases in which molecular genetic analysis had been performed. More cases need to be analyzed to determine if clustering to particular chromosomal bands occurs in variant translocations, and whether APL cases harboring complex 15;17 variants differ clinically from those with classical 15;17 translocation.