伴有t(8;21)的急性髓系白血病研究进展

伴有染色体t(8;21)(q22;q22)易位及AML1-ETO融合基因是急性髓系白血病(AML)的独立亚型,预后较好.虽然以大剂量阿糖胞苷(HD Ara-C)为主的联合化疗在t(8;21)-AML取得了较高的缓解率,但是特异性靶向AML1-ETO的治疗方案可能是治愈该类AML的有效策略.现就AML1-ETO融合基因相关研究及其靶向治疗的研究进展进行综述.     

伴有t(8;21)的急性髓系白血病研究进展

伴有染色体t(8;21)(q22;q22)易位及AML1-ETO融合基因是急性髓系白血病(AML)的独立亚型,预后较好.虽然以大剂量阿糖胞苷(HD Ara-C)为主的联合化疗在t(8;21)-AML取得了较高的缓解率,但是特异性靶向AML1-ETO的治疗方案可能是治愈该类AML的有效策略.现就AML1-ETO融合基因相关研究及其靶向治疗的研究进展进行综述.     

t(8;21)阳性急性髓系白血病伴嗜碱粒细胞增多二例

患者女,17岁.患者于2个月前无诱因出现皮肤淤点、淤斑,伴轻微咳嗽,未在意,于9月26日出现鼻出血、头晕、乏力、活动后气促伴经期延长,遂于2006年9月30日就诊于我院.     

伴t(8;21)的急性髓系白血病近期疗效分析

目的研究影响伴t（8;21）急性髓系白血病（AML）近期疗效的因素。方法将可评判疗效的70例伴t（8;21）AML患者根据诱导治疗的疗效分为二组,A组为标准诱导治疗1—2疗程后CR患者和加用中剂量阿糖胞苷（Ara—C）方案治疗后CR患者;B组为经上述治疗后NR患者。对比二组患者性别、年龄、血象、骨髓象、染色体的差异,寻找影响近期疗效的因素。结果B组患者起病时外周血原始细胞比例、骨髓中原始细胞比例明显较A组高（P〈0．05）,而骨髓中异常中幼粒的比例B组却低于A组（P〈0.05）。3例给予了中剂量Ara-C方案诱导治疗的患者,均取得了缓解。结论伴t（8;21）的AML患者起病时外周血及骨髓中原始细胞比例越高,诱导治疗缓解率越低;而骨髓中异常中幼粒比例越高,诱导治疗缓解率也越高。中剂量Ara—C方案可能会提高伴t（8;21）的AML患者诱导缓解率。     

t(8;21)急性髓系白血病患者MICM分型及预后的回顾性分析

 目的　分析t(8;21)急性髓系白血病（AML）患者的细胞形态学、免疫表型、遗传学、分子生物学（MICM）分型及临床治疗疗效。方法　运用瑞特染色法、FAB细胞形态分类标准、流式细胞术（FCM）直接免疫荧光标记技术、遗传学染色体吉姆萨显带技术及RT-PCR技术对70例确认有t(8;21)与AML1-ETO融合基因双阳性的AML患者及70例正常染色体核型的AML患者进行分析和比较。结果　70例t(8;21)AML患者中M1 1例,M2 64例,M4 3例,无法分型的急性白血病（AL）2例;免疫表型分析发现CD13、CD33、CD34、CD117高表达,40 %表达CD19,11 %表达CD15,10 %表达CD11b,7 %表达CD7;遗传学显示50 %的t(8;21) AML患者有附加染色体异常,主要为性染色体丢失、9q-及超二倍体;RT-PCR检测AML1-ETO融合基因100 %阳性。CD+19 t(8;21) AML患者完全缓解（CR）率72 %,CD+19伴CD+7 t(8;21)AML患者CR率为0,正常核型CR率31 %。结论　t(8;21) AML患者主要在M2中集中出现,附加染色体异常较多见。CD19表达较高,而CD7表达极低,CD34、CD117高表达,这些抗原的表达可能与核型密切相关。CD+19 是预后良好的指标,但同时出现CD+7,则预后不良。     

23例t(8;21)急性粒细胞白血病临床观察

对２３例ｔ（８；２１）阳性急性粒细胞白血病患者进行临床观察，结果表明∶ＡＭＬ１－ＥＴＯ融合基因可作为急性粒细胞白血病Ｍ２ｂ亚型的分子标志物；ｔ（８；２１）阳性急粒化疗疗效与其他类型急性白血病相似；肝脾肿大是预后不良因素之一。     

t（8;21）阳性急性髓系白血病伴嗜碱粒细胞增多一例

患者女,17岁。患者于2个月前无诱因出现皮肤淤点、淤斑,伴轻微咳嗽,未在意,于9月26日出现鼻出血、头晕、乏力、活动后气促伴经期延长,遂于2006年9月30日就诊于我院。查体：贫血貌,皮肤黏膜散在瘀点、瘀斑,胸骨压痛阳性,双颈部淋巴结肿大,肝未触及,脾大肋缘下3cm;     

23例t（8;21）急性粒细胞白血病临床观察

对２３例ｔ（８；２１）阳性急性粒细胞白血病患者进行临床观察，结果表明：ＡＭＬ１－ＥＴＯ融合基因可作为急性粒细胞白血病Ｍ２ｂ亚型的分子标志物；ｔ（８；２１）阳性急粒化疗疗效与其他类型急性白血病相似，肝脾肿大是预后不良因素之一。     

有助于t(8;21)急性髓细胞白血病的诊断和预后判断的免疫表型特征

 t(8;21)核型急性髓细胞白血病（AML）是临床常见类型白血病,更多见于FAB分型M2型。由于21号染色体上的AML1基因和8号染色体上的ETO基因发生融合,而产生AML1-ETO融合蛋白。t(8;21) AML具有独特的免疫表型,这些独特的免疫表型特征不仅有助于t(8;21) AML的诊断,而且决定了t(8;21) AML的预后     

Biologic activity of triptolide in t(8;21) acute myeloid leukemia cells

Triptolide is a compound isolated from the traditional Chinese medicinal herb Tripterygium wilfordii that shows potent anti-tumor activities, but its effects on acute myeloid leukemia with t(8;21) remain unclear. Here we report that triptolide inhibits cell proliferation and induces apoptosis in a dose- and time-dependent manner of t(8;21)-bearing Kasumi-1, SKNO-1 and CD34+ cells harvested from bone marrow samples of patients with t(8;21) leukemia. We show that triptolide triggers cleavage of the resultant AML1-ETO fusion protein of t(8;21), and causes downregulation of C-KIT followed by inhibition of JAK-STAT signaling. Triptolide downregulates p65 and inhibits the DNA-binding activity of NF-κB. Our data indicate that triptolide might be an effective agent for t(8;21) leukemia.     

Hematological features and treatment outcome in acute myeloid leukemia with t(8;21)

We analyzed the hematological features and treatment outcome in 18 patients with t(8;21) acute myeloid leukemia (AML) diagnosed in Queen Mary Hospital, Hong Kong. They comprised 15 cases of M2, two cases of M4 and one case of M1 according to FAB criteria. Auer rods (17 cases) and dysgranulopoietic features (15 cases) were very frequently observed. Two cases showed marrow eosinophilia while blast cells in one patient demonstrated erythrophagocytic activity. Chromosome changes in addition to t(8;21) were seen in 14 patients, the most common of which was loss of a sex chromosome (10 cases). Of the 14 patients treated with intensive chemotherapy, 13 (93 per cent) entered complete remission with a median event-free survival (EFS) and overall survival (OS) of 11 and 24 months respectively. The probability of EFS and OS at 3 years were 33±14·3 per cent and 55·1±15·6 per cent respectively with a median duration of follow-up of 22 months. When compared with AML having no t(8;21) treated similarly in the same period, we could not demonstrate a better clinical outcome for t(8;21) AML. © 1997 John Wiley & Sons, Ltd.     

Acute myelogenous leukemia with t(8;21)--identification of a specific immunophenotype

Association between certain surface markers and acute myelogenous leukemia (AML) with t(8;21) has been described. The specificity and the predictive values of these markers have never been assessed. In this study, we aimed, to explore whether a specific pattern could predict for this translocation. Of 405 consecutive AML, 18 (4.4%) had the t(8;21). Patients with this cytogenetic abnormality showed higher frequency of CD34 (P = 0.003), HLA-DR (P = 0.03), Tdt (P = 0.02), CD19 (P < 0.0001), and CD56 (P < 0.0001) and lower CD33 (P = 0.0001). Taken singly, the sensitivity of these markers for AML with t(8;21) ranged between 39 and 100% with CD34+ having the highest and CD33- having the lowest and the positive predictive values (PPV) ranged between 5 and 21% with CD19+ having the highest and HLA-DR+ having the lowest. When combinations of different markers were analyzed by multivariate analysis, the pattern CD34+/HLA-DR+/MPO+ was found to have the highest sensitivity (100%) with a PPV of 14% and the pattern CD34+/CD19+/CD56+ had the highest PPV (100%) with a sensitivity of 67%. We conclude that AML with t(8;21) is better identified by a combination of markers than by a single antigen pattern, the absence of CD34+, HLA-DR+ or MPO+ would preclude and the expression of the pattern CD34+/CD19+/CD56+ is highly predictive and could serve as a screening criteria for the t(8;21).     

伴4号染色体三体异常的t（8；21）急性髓系白血病c-kit基因突变的发生及患者预后

目的：探讨伴有4号染色体三体异常的t（8;21）急性髓系白血病（AML）c-kit基因突变的发生率及患者预后。方法回顾性分析2005年2月至2013年1月145例初治t（8;21）AML患者的实验室及临床资料。所有骨髓样本均采用R显带技术进行核型分析。采用PCR方法检测c-kit基因8号、17号外显子突变情况,并分析患者的临床预后。结果145例t（8;21）AML患者中,12例（8.3%）伴有4号染色体三体异常,其c-kit基因突变发生率为91.7%（11／12）,明显高于其他患者[26.3%（35／133）]（P＜0.01）。生存分析显示,伴有4号染色体三体异常的t（8;21）AML患者的3年总体生存（OS）率及无病生存（DFS）率（15%、0）均低于其他t（8;21）AML患者（56%、51%）（P＜0.01）。同时伴有4号染色体三体及c-kit基因突变的t（8;21） AML患者的OS率及DFS率均较不伴有或不同时伴有4号染色体三体及c-kit基因突变的患者低（均P＜0.05）。结论伴有4号染色体三体异常的t（8;21）AML患者c-kit基因突变发生率高,且预后不佳。4号染色体三体异常或联合c-kit基因突变是影响t（8;21）AML患者生存的主要因素。