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.     

隐匿型t(15;17)易位伴inv(11)(p12q23)核型的急性早幼粒细胞白血病

为进一步探讨无ｔ（１５；１７）易位而伴有其它染色体改变的急性早幼粒细胞白血病（ＡＰＬ）患者分子生物学变化与预后的关系，应用短期细胞培养、胰酶消化、Ｇ显带技术进行骨髓细胞染色体检测及使用巢式ＲＴ／ＰＣＲ技术检测ＰＭＬ／ＲＡＲａ融合基因及ＨＲＸ基因。在被检测的３２例ＡＲＬ患者中，发现１例４６，ＸＸ，ｉｎｖ（１１）（ｐ１２ｑ２３），无ｔ（１５；１７）易位的ＡＰＬ患者。分子生物学见ＰＭＬ／ＲＡＲａ融合基因转录本，未见ＨＲＸ基因重排。该患者使用全反式维甲酸诱导治疗１０５天，无缓解征象，改用ＨＯＡＰ方案化疗也未显效。     

慢粒患者经格列卫治疗后细胞遗传学改变:标准Ph易位t(9;22)(q34;q11)变为变异Ph易位t(21;22)(p11;q11)

目的通过对慢性粒细胞白血病(chronic myeloid leukemia,CML)患者经格列卫药物治疗后细胞遗传学改变的研究,探讨ABL-BCR的表达缺失与获得性格列卫耐药的关系。方法应用R显带技术对染色体进行核型分析,并选用BCR/ABL探针,通过双色荧光原位杂交技术进一步确认遗传学分析。结果患者经格列卫治疗后染色体核型由t(9;22)(q34;q11)变为t(21;22)(p11;q11)。双色荧光原位杂交证实此患者核型应为46,XY,t(9;22;21)(q34;q11;p11)。结论变异Ph易位中ABL-BCR的表达缺失与获得性格列卫耐药有关,荧光原位杂交技术在检测变异易位中起重要作用。     

FISH在免疫表型特殊的急性早幼粒细胞白血病诊断中的应用

为探讨荧光原位杂交(fluoresence in situ hybridization,FISH)技术在免疫表型特殊的急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)诊断中的应用,作者用流式细胞仪(flow cytometry,FCM)检测APL患者骨髓中单个核细胞的免疫表型,并用FISH检测患者是否存在PML/RARα融合基因.结果发现,少数APL患者免疫表型为CD13 ,CD33 ,CD34-和HLA-DR ,而利用FISH技术检测后,发现存在PML/RARα融合基因,与典型的APL患者HLA-DR-、PML/RARα融合基因( )的结果不同,提示临床上不能只将免疫表型作为诊断白血病的独立指标,而应该结合传统的FAB分型及新兴的分子诊断技术如FISH、PCR等来协助诊断.     

荧光原位杂交技术在诊断变异Ph易位及Ph(一)慢性髓细胞白血病中的应用

目的 探讨荧光原位杂交(fluorescence in situ hybridization,FISH)技术在诊断变异Ph易位及Ph(-)慢性髓细胞白血病(chronic myelocytic leukemia,CML)中的应用价值.方法 应用常规R显带方法,对9例伴有变异Ph易位和2例Ph(-)CML患者采用双色双融合bcr/abl探针进行FISH检测.结果 9例变异Ph易位CML患者异常核型除涉及9和22号染色体外,还涉及1、3、5、12、13、15、17、21号染色体,且部分类型为重现性异常,FISH结果均为阳性,信号特征为2R2G1Y;2例Ph(-)CML患者核型正常,FISH结果阳性,信号特征分别为1R1G2Y和1R1G1Y.结论 FISH技术对伴有变异Ph易位及Ph(-)CML患者的诊断更具有优势,可根据阳性细胞信号特征分析其异常核型,判断标记基因异常改变情况,是常规染色体显带分析的有益补充.     

伴变异型Ph易位的慢性髓细胞白血病的分子遗传学研究

目的探讨荧光原位杂交（fluorescence in situ hybridization，FISH）及多重荧光原位杂交（multiplex FISH．M-FISH）技术在检测伴变异型Ph易位（variant philadelphia translocation，vPh）的慢性髓细胞自血病（chronic myeloid leukemia，CML）中遗传学改变的意义。方法对10例常规R显带显示伴vPh的CML以双色双融合FISH技术检测其染色体标本。对于间期细胞中仅有单个融合信号的标本，观察其中期细胞，以确定是否为衍生9号染色体[der（9）]缺失。同时对这10例CML进行M—FISH技术检测。结果FISH技术在10例伴vPh的CML中检测到5例存在der（9）缺失。M—FISH检测到除22号染色体外，1、3、5、6、8、10、11和17号染色体也参与vPh，发现了常规细胞遗传学未发现的异常，包括2种未见报道的异常。结论对伴vPh的CML联合使用常规细胞遗传学、FISH、M—FISH技术可使遗传学诊断更加完善。     

伴22三体急性髓系白血病的inv(16)FISH研究

目的 探讨伴有22三体(+22)的急性髓系白血病(acute myeloid leukemia,AML)中inv(16)的发生率,以及inv(16)荧光原位杂交(interphase fluorescence in situ hybridization,FISH)检测对于+22AML的临床意义.方法 采用红、绿荧光素直接标记的双色断裂点分离的CBFβ基因探针对19例核型分析中伴有+22克隆件异常的AML患者进行间期FISH检测,并与常规细胞遗传学分析结果进行比较.结果 19例+22AML,中FISH检测发现13例(68.4%)为CBFβ重排阳性,包括M4EO 7例,M5 3例,M2a 2例,M1 1例;6例患者CBFβ重排为阴性,包括t(8;21)M2 1例,t(6;11)M5 1例,复杂核型异常2例,不伴有其他异常而以+22作为唯一异常的M2 2例.14例的随访资料显示CBFβ重排阳性的11例中10例尚存活,仅1例死亡,而CBFβ重排阴性的3例均已死亡.结论 +22为inv(16)AML最常见的继发性改变,因此有预测inv(16)AML的价值,+22AML的预后与inv(16)而不是与+22本身相关;FISH检测不仅对于确诊inv(16)有重要价值,而且有助于明确+22AML的预后.     

21例伴有4号染色体三体细胞的急性白血病的分析

目的探讨伴有4号染色体三体细胞的急性白血病（acute leukemia，AL）的临床和实验室特点。方法对21例伴有4号染色体三体细胞的AL患者的临床和实验室资料进行回顾性分析。21例均采用骨髓细胞直接法或短期培养法制备染色体，用R显带技术进行核型分析；其中5例核型分析揭示t（8；21）易位者，采用AMLl／EqO双色探针和间期荧光原位杂交技术进行AMLl／ETO重排检测；应用SpectrumGreen标记的4号着丝粒探针，对其中13例AL患者进行荧光原位杂交检测。结果21例AL中2例为继发性白血病，其余均为原发性白血病。4号染色体三体异常主要见于AML-M2（9／21例），21例中7例为单纯4号染色体三体，14例同时伴有其他异常，以t（8；21）最常见（8／14例）；临床上16例初诊白细胞计数大于10×10^9／L；15例有不同程度的肝、脾和淋巴结肿大；进行免疫表型分析的15例患者中6例为髓系和淋系抗原共表达，11例有CD34表达。双色荧光原位杂交研究揭示其中5例核型分析显示t（8；21）者均有AMLl／EqO重排，单色荧光原位杂交也证实14例为4号染色体三体阳性。结论伴有4号染色体三体异常的急性白血病有着独特的临床和实验室特点，其预后不良。     

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。     

Acute promyelocytic leukemia with cryptic t(15;17) on isochromosome 17: a case report and review of literature

Acute Promyelocytic Leukemia (APL) is one of the most curable leukemia which shows great sensitivity to all-trans retinoic acid (ATRA) although a small number of the patients present poor prognosis and short survival. Isochromosome 17 in APL which usually bears an additional copy of RARA/PML fusion gene is considered to be a negative factor on its prognosis. Cryptic t(15;17) on i(17q) leads to an extra copy of PML/RARA rather than RARA/PML which may confer a worse prognosis. We describe here a rare APL case with complex chromosomal abnormality including isochromosome 17 bearing cryptic t(15;17) showing poor outcome. The patient lacks a classic t(15;17) and fluorescence in situ hybridization (FISH) presents 2 PML/RARA fusion signals on both long arms of the isochromosome. The patient also acquired a secondary mutation at relapse when the initial karyotype was already a complex karyotype involving chromosome 13, 17 and 22 at the same time. The poor response of this patient to traditional chemotherapy like ATRA and novel therapy like arsenic trioxide (ATO) suggests that early auto-hematological stem cell transplantation may be the choice of APL with isochromosome 17 especially with cryptic t(15;17) on i(17q). We are the first to show a clear history and evidence of FISH of these kind of cases. A small summary of cases with cryptic t(15;17) on isochromosome 17 is also made.     

The comparison of bone marrow kinetics between patients with acute myeloid leukemia and acute promyelocytic leukemia after induction chemotherapy

Abstract

Background and Aim: Recently, acute promyelocytic leukemia (APL) has shifted from the most hazardous to the best curable type of acute myeloid leukemia. Anthracyclines, all-trans retinoic acid (ATRA) and arsenic derivatives are the most important developments for the treatment of APL. ATRA promotes the terminal differentiation of malignant promyelocytes to mature neutrophils. We aimed to compare platelet and neutrophil recovery time after induction chemotherapy in patients with acute myeloid leukemia (AML) and APL.

Materials and Methods: Two hundred and fifteen patients with AML and APL, who were diagnosed and treated in our tertiary care center between the years of 2001 and 2018 were evaluated.

Results: One hundred and eighty one AML patients (84.2%) and 34 (15.8%) APL patients were included in this study. The time between neutrophil nadir after induction chemotherapy and neutrophil recovery was longer in APL patients than in AML patients [30.5 (4–52) vs. 20 (5–58), p?<?0.001]. The time between platelet nadir after induction chemotherapy and platelet recovery was longer in APL patients than in AML patients [21.5 (4–42) vs. 17 (4–45), p?=?0.02].

Conclusion: Neutrophil and platelet recovery times were longer in APL patients than in AML patients in our present study. In 60?days, mortality rate was higher in APL patients than AML patients. Non-relapse mortality (NRM) rate was similar between two groups. There was a significant difference between two groups in terms of NRM causes. Platelet and neutrophil recovery time is very important because infection is the most important cause of NRM.     

Tetraploidy acute promyelocytic leuemia with double t(15;17)/PML-RARA,a case report with review of literature

Acute promyelocytic leukemia (APL) with tetraploidy chromosome harboring t(15;17)(q23;a21) is extremely rare. To date, there are 14 such cases reports that describe this entity, mostly found in Eastern hemisphere. Herein we described a 51-year-old man with a diagnosis of tetraploid acute promyelocytic leukemia with double (15;17) translocations and compare the prototypically clinicopathologic, genetic and molecular findings with those reported in the literature.