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TKI治疗时代成人Ph+急性淋巴细胞白血病p190和p210两种不同转录本的临床特征及预后等差异分析
目的:分析酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗时代Ph+急性淋巴细胞白血病(Ph+acute lymphocytic leukemia,Ph+ ALL)两种转录本p190和p210的临床特征及预后等差异,为该类疾病的临床预后分层和个体化治疗提供依据方法:回顾性分析2005年1月至2014年12月在我院诊断为Ph+ ALL且使用常规化疗加TKI治疗伴或不伴造血干细胞移植(HSCT)的65例患者临床资料,对比研究p190(n =41)和p210(n =24)两种不同转录本的临床特征及预后差异.结果:在临床特征上,p190组血小板数低于p210组,虽未达到显著性统计学差异,但却具有较为明显的差异趋势(46.3 × 109/L vs 65×109/L) (P =0.084);另外可见p190组初治骨髓样本中幼稚细胞比例较p210组有增高趋势(88.4％ vs 76.8％)(P=0.096);其他临床特征如性别,年龄,白细胞,血红蛋白,外周血幼稚细胞比例,BCR-ABL/ABL表达水平等,在两组间未见明显差异.在治疗反应上,p190组和p210组在诱导治疗后完全缓解(complete remission,CR)率分别为80％(32/40)和87％ (20/23),无明显差异(P=0.732);诱导至第1次完全缓解(the first complete remission,CR1)所需时间也无明显差异(28 vs 29 d)(P=0.922),两组完全缓解后复发率分别为61％(20/33)和43％(9/21),虽未见明显统计学差异(P =0.202),但p190组的复发时间早于p210组,无论是从确诊时间起(212 vs 274 d)(P=0.077)还是从CR1时间起(146 vs 242 d)(P=0.084).在预后方面,p190组较p210组有较差的5年总生存(P=0.016)和无事件生存(P=0.085).结论:p190组较p210组具有血小板数偏低,初治骨髓血幼稚细胞数偏高的特点;CR率、CR1所需时间无明显差别,但p190组较易复发且复发时间较早,且5年总生存及无事件生存差于p210组,提示p190阳性患者在CR1后需尽快采取造血干细胞移植等强化治疗,以减少早期复发,进而改善Ph+ ALL病人的整体预后.
关键词： Ph+急性淋巴细胞白血病 酪氨酸激酶抑制剂 BCR-ABL p190 p210 -
以bcr/abl mRNA及P210为靶点治疗慢性髓系白血病的新进展
慢性髓系白血病(CML)起源于多能干细胞的肿瘤性转化, 其特点是白细胞总数增加,骨髓及血液中髓系各期细胞显著增多,以中、晚幼粒细胞尤甚.一般经过3～5年的慢性期,恶化为加速期、急变期终死亡.常规治疗用细胞毒药物及干扰素,可改善临床症状,达到血液学缓解,延长生存期,但不能阻止疾病向急变发展.自体造血干细胞移植(ASCT)复发率高.异基因造血干细胞移植是当前惟一可能治愈CML的方法,但受供体来源及患者年龄的限制,仅少部分患者有机会得以实施,限制了在临床上的广泛应用.
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伊马替尼、5-溴汉防己甲素逆转K562/A02细胞多药耐药的研究
Background and Objective: Research has shown that 5-bromotetrandrine (BrTet) can effectively reverse multidrug resistance (MDR). Imatinib plays an important role in cell proliferation. This study explored the efficacy of the combination of imatinib and BrTet on reversing MDR of tumor cells and its mechanism. Methods: Cytoxicity was assessed by MTT assay. Apoptosis of K562/A02 cells was analyzed by flow cytometry. The expressions of mdr1 mRNA and P-glycoprotein (P-gp) were detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results: After 48 h of treatment with 0.0625 umol/L imatinib, 0.5 umol/L BrTet, or both, the 50% inhibition concentration (IC50) of daunorubicin (DNR) for the K562/A02 cells were 5.69 mg/L, 5.41 mg/L, and 2.19 mg/L, respectively. The gray-scale values of mdr1 mRNA expression in the K562/A02 cells were 0.65 ± 0.02, 0.64 ± 0.01, and 0.25± 0.03, respectively. The expression levels of P-gp were 0.74 ± 0.02, 0.52 ± 0.02, and 0.29 ± 0.02, respectively. All decreased significantly in the K562/A02 cells treated with both imatinib and BrTet compared to cells treated with imatinib and BrTet alone (P < 0.05). The apoptosis rates of the K562/A02 cells increased without a significant difference after treatment with DNR, imatinib, or BrTet (P > 0.05), while increased significantly after treatment with DNR combined with imatinib, BrTet, or both (P < 0.05). Conclusions: The MDR of K562/A02 cells may be partially reversed by imatinib or BrTet, and the mechanism may be related to the downregulation of mdr1 mRNA and P-gp expression and the upregulation of the rate of apoptosis in K562/A02 cells. Imatinib combined with BrTet showed a synergistic effect on K562/A02 cells.
