儿童急性白血病形态学免疫学和细胞遗传学的分型诊断

目的：准确地进行儿童急性白血病（AL）的诊断分型,提高初诊患儿的诊断符合率。方法：采用形态学、免疫学和细胞遗传学（MIC）相结合的诊断方法,分析了110例初诊为AL的患儿。结果：形态学与MIC分型诊断符合率为88．2％;急性淋巴细胞性白血病（ALL）免疫分型诊断符合率为92．2％;而急性髓细胞性白血病（AML）仅为62．9％。8／35例AML表达淋系抗原（1y^ -AML),12／59例ALL表达髓系抗原（My^ -AML);11／110例为杂合性白血病。染色体核型异常检出率为63．6％。t(8;21）易位见于（13／21例）M2;t(7;11）易位见于12例M2;t（15;17）易位见于（2／5例）M3;t（9;22）和t（4;11）易位见于（8／64例）ALL。结论：运用MIC诊断分型方法能提高儿童AL的诊断率,为AL个体化治疗和评估预后提供信息。     

慢性髓细胞白血病急变期形态学及免疫学和细胞遗传学特征研究

目的：探讨慢性髓细胞白血病急变期（CML－BC）的形态学、免疫表型和细胞遗传学法及流式细胞仪进行细胞免疫分型,细胞遗传滂采用直接法或短期培养法制备染色体标本,采用R显带技术进行核型分析。结果：免疫分型结果显示：急变为急性髓细胞白血病（AML）23例占74．2％;急性淋巴细胞白血病（ALL）5例占16．1％,均为B系ALL,其中4例同时伴有髓系表达;急性未分化细胞白血病1例,B系和髓系急性混合细胞白血病（AMLL）2例。31例CML－BC中21例（67．7％）的急变患者CD34^ ,其中4／5（80．0％）ALL,15／23（65。2％）,2／2AMLL均为CD34^ 。AML急变患者中具有CD7和CD34共表达者为8／23（占34．8％）。细胞遗传学分析表明,14／27（51．9％）和急变期患者出现Ph染色体以外的附加核型异常,其中有＋8（3／14）,＋Ph(3/14),i(17q)(2/14),Y染色体丢失（1／14）及复杂易位5／14）。结论：CML－BC是一干细胞疾病,原始细胞分化阻滞在早期阶段,故预后差。MIC分型在CML－BC诊断,预后判断及指导治疗方面均有重要价值。     

形态学、免疫学、细胞遗传学联合检测诊断急性白血病的临床意义

为探讨形态学、免疫学、细胞遗传学联合检测对急性白血病(AL)诊断、治疗、预后判断等方面的临床意义，对初诊为AL的39例患者分别进行了骨髓细胞形态学、免疫学及染色体检测。并按照FAB标准进行形态学(组织化学染色)分型；采用间接免疫荧光法标记活细胞膜表面分化抗原(CD)进行免疫学分型；采用24小时培养法制备染色体标本，G带显示法进行染色体检查。结果：39例患者经形态学检查确诊为AL，其中急性淋巴细胞白血病(ALL)8例，急性非淋巴细胞白血病(ANLL)29例，2例难以分型；免疫学诊断为ALL8例(其中2例伴髓系抗原表达)，ANLL29例(其中4例伴淋巴细胞抗原表达)，2例形态学难以分型者，诊断为急性杂合性白血病。免疫学与形态学分型符合率94．9％(37／39)。39例中染色体核型异常18例。本研究结果还显示，经临床治疗后染色体复杂畸形者缓解率低，正常核型及某些染色体核型[如t(15；17)]者缓解率较高。认为形态学、免疫学、细胞遗传学联合检测可提高AL诊断的准确性，有助于制定治疗方案及判断预后。     

11q23少见染色体易位同时具有t（8；21）的急性白血病1例报告并文献复习

目的:报道13号染色体为11q23伙伴染色体的急性髓系白血病(AML)1例,该例患者同时具有t(8;21)染色体易位。方法:用R显带技术进行核型分析。结果:染色体核型分析结果为45,x,-y,t(8;21)(q22;q22),t(11;13)(q23;q13)[5]/44,x,-y,t(8;21),t(11;13)[CP5]。结论:13号染色体为11q23少见的伙伴染色体,国内迄今未见报道,国外报道4例。同时具有11q23异常和t(8;21)的急性白血病,国内文献中尚未见到这种病例。同时具有2个特异的细胞遗传学异常的AML有可能为一新的临床遗传学类型。     

急性淋巴细胞性白血病的细胞及分子遗传学研究进展

随着常规细胞遗传学及分子诊断技术的迅速发展，人类对白血病遗传学基础的认识有了巨大的飞跃，染色体异常的检出率不断提高，相关基因的研究也更加深入。染色体核型是急性淋巴细胞性白血病(ALL)的一个独立预后因素，细胞及分子遗传学特征已成为影响治疗选择的重要因素。ALL患者染色体核型通常质量较差，但是异常核型的检出率约70％，且许多为复杂核型。ALL染色体异常包括数目及结构异常，部分患者可同时检出两种异常。     

慢性髓细胞性白血病骨髓移植后细胞遗传学动态观察

本文报道12例慢性髓性白血病(CML)患者骨髓移植(BMT)后染色体系统的追踪概况。BMT后三种核型:1.完全供者细胞;2.正常供者/受者或供者/受者Ph(+);3.正常供者/受者/受者Ph(+)细胞。BMT后1例病人复发,染色体伴有附加异常+(18,21)、t(4;15)、b13q、15q~+、8q~+。附加异常为研究移植后细胞遗传学能否帮助新型染色体核型及与复发的关系有重要意义。     

急性髓细胞白血病表达CD7抗原的临床意义以及与细胞遗传学的相关性

目的：了解急性髓细胞白血病（AML）表达CD7抗原的临床意义以及与细胞遗传学的相关性。方法：对我院诊治的52例AML患者的免疫表型、细胞遗传学以及临床特点进行分析。结果：15例（28．8％）患者的骨髓白血病细胞表达CD7抗原。根据FAB分型,M2（18．5％）和M。型（20％）的CD7^＋率较低。CD7^＋组早期细胞抗原CD34、HLA—DR、CD117的表达率以及老年患者（大于60岁）比例高于CD7^-组,白细胞计数、染色体异常率、肝脾肿大及髓外白血病发生率均低于CD7^-组。CD7^＋组完全缓解（CR）率高于CD7^-组,无病生存期（DFS）短于CD7组,但差异均无统计学意义（P〉0．05）。70％以上的CD7^＋ AML患者分布在中等预后核型组。随着预后好、预后中等、预后差核型组的变化,AML所有病例、CD7^-组、CD7^＋组的CR率均呈逐渐下降趋势。结论：与CD7^- AML相比,CD7^＋ AML更容易获得CR,可能与低的白细胞计数、低的染色体异常率以及低的肝脾肿大与髓外白血病发生率有关;CD7^＋ AML患者年龄较大或同时表达早期细胞抗原,可能影响DFS。AML无论是否表达CD7抗原,染色体核型是判断预后最重要的因素。     

伴有t（2；8；21）（p12；q22；q22）复杂易位的急性髓系白血病的实验研究

目的探讨伴有t（2;8;21）（p12;q22;q22）染色体复杂易位的急性髓细胞白血病M2（AML-M2）的实验室特征。方法通过骨髓涂片进行细胞形态学分析诊断;流式细胞仪分析免疫表型;采用RT-PCR检测AML1-ETO融合基因;通过R显带进行常规染色体核型分析;双色荧光原位杂交明确染色体易位。结果细胞形态学诊断为AML-M2,流式分析细胞表达髓系抗原,AML1-ETO融合基因为阳性;染色体常规核型分析及FISH结果显示t（2;8;21）（p12;q22;q22）三联复杂易位。结论t（2;8;21）（p12;q22;q22）是一种罕见的（8;21）（q22;q22）复杂变异易位。综合形态学、免疫学、细胞遗传学和分子生物学诊断分析白血病,有助于全面评价疾病的预后,并为临床实施个体化治疗方案提供实验室依据。     

急性髓系白血病M4/M5亚型的临床和遗传学研究

目的研究伴11q23异常的急性粒单细胞和单核细胞白血病患者的临床和细胞遗传学特征。方法用染色体G显带和间期荧光原位杂交技术对30例急性髓系白血病（AML）-M4、M5患者进行染色体检测,患者均接受柔红霉素、阿糖胞苷为主的化疗方案,并对其随访。结果伴11q23异常13例,其中M59例（M5a1例、b15b8例）、M4b5例;异常核型为t（11;19）、t（11;17）、t（9;11）、t（10;11）、t（6;11）、t（11：？）（q23：）、del（11）（q23）。混合细胞白血病（MLL）基因阳性13例,其中hi58例、hi45例,其完全缓解（CR）率15．4％,低于MLL阴性者的57．0％;MLL阳性者中位生存期85d,低于MLL阴性者的130d。结论11q23异常以MLL．hi5、hi4患者发生率高,MLL阳性者CR率低,平均生存期短。提示MLL基因异常是MLL患者预后不佳的标志。     

老年急性髓系白血病患者106例临床特点

目的 研究急性髓系白血病老年患者细胞遗传学及分子生物学特征.方法 回顾性分析我中心初治老年急性髓系白血病患者106例,对其的染色体核型及基因突变进行研究.结果 106例患者中异常核型52例,检出率为49.06％.t(15;17)及t(8;21)预后良好核型的发生率分别为13.21％ (14/106)与5.66％ (6/106);预后不良的复杂核型及单体型核型的检出率分别为9.43％ (10/106)及4.72％ (5/106).染色体预后分层:良好组、中危组、高危组所占比例分别为18.87％ (20/106)、70.75％ (75/106)与10.83％ (11/106).高危组预后较差.共21例患者行分子学检测,NPM1、FLT3-ITD及c-kit突变的发生率分别为23.81％、14.29％及4.76％,NPM1、FLT3-1TD突变者均为正常核型,c-kit突变只见于t(8;21)患者.结论 老年患者预后良好核型低,预后不良核型则高.老年患者预后较差,高危组患者预后更差.     

Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review

Chromosome 7 abnormalities in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) heralds a poor prognosis. However its prevalence, morphological characteristics and clinical impact in MDS and AML in Indian subcontinent is sparsely reported. This was an observational cross-sectional study performed to evaluate the clinico-pathological profiles of MDS/AML patients with chromosome 7 abnormalities over a period of 4 years. 724 cases of MDS (n?=?150) and AML (n?=?574) were evaluated. Abnormal karyotype was detected in 49% (43/88) patients of MDS and 44% (127/289) cases of AML. Chromosome 7 abnormalities were detected in 18% cases of MDS (16/88) and 6.5% (19/289) cases of AML. Sole chromosome 7 abnormalities were detected in 5.7% (5/88) and 2.7% (8/289) and in adjunct to complex abnormalities in 7.9 and 3.1% cases of MDS and AML respectively. Morphologically, dyserythropoiesis, dysmyelopoiesis and eosinophilia were seen in 100, 66 and 56% cases of MDS and 38, 40 and 21% cases of AML. Majority of the patients had an aggressive natural course and outcome was dismal. Chromosome 7 abnormalities are strongly associated with the presence of morphological dysplasia and eosinophilia, irrespective of the type of aberration. It is invariably associated with very poor outcome.     

AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence,partner chromosomes,FAB subtype,age distribution,and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases

Acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene comprise one category of recurring genetic abnormalities in the WHO classification. In an unselected series of 1897 AML cases, 54 patients with an 11q23/MLL rearrangement were identified, resulting in an incidence of 2.8%. The incidence of AML with MLL rearrangement was significantly higher in therapy-related AML (t-AML) than in de novo AML (9.4% vs 2.6%, P <.0001). The frequency of MLL rearrangements was significantly higher in patients younger than 60 years (5.3% vs 0.8%, P <.0001). While the incidence of MLL rearrangements in AML M4, M5a, and M5b was 4.7%, 33.3%, and 15.9%, respectively, it was found in only 0.9% of all other French-American-British (FAB) subtypes (P <.0001). Compared with AML with intermediate karyotype, AML with 11q23/MLL rearrangement had a worse outcome, which was rather comparable with AML with unfavorable karyotype. Compared with t-AML, the median overall survival (OS) of de novo AML with MLL rearrangement was significantly better (2.5 vs 10 months, P =.0143). No significant differences in median OS were observed between cases with t(9;11) compared with all other MLL rearrangements (10.0 vs 8.9 months, P =.36). In conclusion, the category AML with 11q23/MLL abnormalities accounts for 2.8% of unselected AML, is closely associated with monocytic differentiation, and has a dismal prognosis. (     

Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities

Acute myeloid leukaemia (AML) cases with different chromosomal abnormalities may reflect different aetiologies. Benzene exposure, from a number of sources including smoking, is one risk factor for AML. Individual susceptibility to benzene may depend on differences in expression of metabolizing enzymes. We tested the hypothesis that smoking as well as genetic polymorphisms in the microsomal epoxide hydrolase gene (HYL1), an enzyme involved in benzene metabolism, could be risk factors for AML with defined chromosomal abnormalities. Twenty-six AML cases with -7/del(7q) and 24 cases with t(8;21), as well as 43 cases with normal karyotype and 155 age-, sex- and residence-matched controls, were drawn from a large case-control study on adult acute leukaemia. Current smoking was significantly associated with the cytogenetic abnormalities t(8;21) or -7/del(7q) (OR = 4.9; 95%CI = 2.1-11.5) but not with a normal karyotype, relative to individuals who were not current smokers. A putative high activity HYL1 phenotype [exon 3, residue 113 (Tyr/Tyr) and exon 4, residue 139 (His/Arg or Arg/Arg)] was associated with a significantly increased AML risk in men with -7/del(7q) or t(8;21) (OR = 4.4; 95%CI 1.1-17.0) but not with a normal karyotype. This suggests that AML cases with defined chromosomal abnormalities could be related to specific carcinogen exposures and, furthermore, suggests that smoking and genetic polymorphisms in HYL1 could be risk factors for AML with -7/del(7q) or t(8;21).     

Prospective study of 174 de novo acute myelogenous leukemias according to the WHO classification: subtypes, cytogenetic features and FLT3 mutations

We report a prospective study of 174 unselected adult de novo acute myeloid leukemia (AML) cases diagnosed using the WHO classification. Of those, 57 (33%) were AML with recurrent cytogenetic abnormalities, 41 were (24%) AML with multilineage dysplasia, 74 (42%) were AML not otherwise categorized, and two were acute leukemias of ambiguous lineage. Clonal cytogenetic abnormalities were detected in 64% of the WHO AML cases with t(15;17) (15%), t(8;21) (12%), +8 (11%), -7/del7q (8%) and del9q (5%) being the most common ones. The FLT3/ITD mutations (FMS-like tyrosine kinase 3/internal tandem duplication) were observed in 12% of the WHO AML cases, which is much lower than ones in the literature, while the 6% incidence of the FLT3-activating loop mutations (either FLT3/D835 or FLT3/I836) was comparable with others. Both mutations were associated with leukocytosis. Our study also suggests that the FLT3 mutations are biomarkers independent of cytogenetic characteristics.     

Two Cases of Secondary Acute Myeloid Leukemia Accompanying Adult T-Cell Leukemia/Lymphoma

We identified 2 cases of secondary acute myeloid leukemia (AML) following adult T-cell leukemia/lymphoma (ATL) in patients who had previously received chemotherapy. Both cases were thought to represent therapy-related AML because the patients had previously received combination chemotherapy including epipodophyllotoxin, anthracycline, and alkylating agents for the ATL. The cases were diagnosed as AML M4 with eosinophilia and AML M2, with the chromosomal abnormalities inv(16)(p13q22) and t(8;21)(q22;q22), respectively. In our hospital, only these 2 cases of secondary AML accompanying ATL were identified among 90 cases of acute- or lymphoma-type ATL diagnosed from October 1999 to July 2006. The frequency of coexisting AML and ATL is lower than that reported for acute leukemia coexisting with other lymphoid malignancies. The low frequency of secondary leukemia with ATL may be associated with the short survival times of ATL patients.     

Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy. The myelodysplastic phase, with or without evolution to acute leukemia, is a highly lethal disease with a median survival comparable to that of the patients who present with AML.     

Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients

BACKGROUND: The FLT3 gene is frequently mutated in acute myeloid leukemia (AML), either by an internal tandem duplication (ITD) of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain (ATKD). Only a few investigations have focused on the prognostic significance of FLT3 alterations in AML among the elderly, yielding conflicting results. In the present study, the frequency and clinical relevance of FLT3 abnormalities were ascertained in a cohort of elderly AML patients. PATIENTS AND METHODS: A total of 109 AMLs, occurring in patients above the age of 60 yr (median 71.5), were investigated. DNA was extracted from fresh bone marrow cells or from cells in fixative and investigated for the presence of ITD of exons 14 and 15 and the ATKD D835 in exon 20. RESULTS: ITDs and ATKDs were identified in 20 (18%) and 11 (10%) of the cases, respectively. Three cases displayed both an ITD and an ATKD. FLT3 abnormalities were associated with leukocytosis (ITD P < 0.01; ATKD P = 0.069), and the monocytic FAB subtypes M4 and M5 [ITD (P < 0.05), ATKD (P = 0.05)], and ITD and ATKD were significantly (P < 0.05) more common in cases with a normal karyotype. There was no correlation between the presence of FLT3 abnormalities and complete remission rates or overall survival. CONCLUSION: A correlation was observed between FLT3 abnormalities and leukocytosis, a normal karyotype, and the M4/M5 subtypes of leukemia. However, no clear-cut prognostic impact of FLT3 abnormalities was identified in elderly AML patients.     

Serial Morphologic Observation of Bone Marrow in Aplastic Anemia in Children

Recent reports of myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) developing after treatment with immunosuppressants and granulocyte colony-stimulating factor (G-CSF) has raised the question of whether previously unrecognized myelodysplastic features had been present or whether actual transformation had occurred. We undertook a multi-institutional study of 112 children with aplastic anemia diagnosed between 1976 and 1996 and then treated with immunosuppressants with or without G-CSF. In each case, bone marrow specimens were tested at study entry and every 6 months for 3 years to detect t-MDS/AML as defined by morphologic and molecular/cytogenetic criteria. As of December 2001, all eligible patients had been followed for a median of 3 years. Morphologic abnormalities were found in 17 cases. The patients in 4 of these cases had clonal cytogenetic abnormalities and received MDS diagnoses. The morphologic features of the patients with and without clonal cytogenetic abnormalities were indistinguishable. However, the mast cell content was lower in cases with cytogenetic abnormalities than in cases without them. An elucidation of the role of mast cells may provide information about the differences between aplastic anemia and MDS or about the transition of aplastic anemia to MDS.