Search

目的 分析经典型BCR-ABL阴性骨髓增殖性肿瘤（MPN）的基因突变及临床特征。 方法 应用二代测序方法检测108例初诊BCR-ABL阴性MPN患者[原发性血小板增多症（ET）55例，真性红细胞增多症（PV）24例，原发性骨髓纤维化（PMF）29例]与疾病相关的127个基因突变情况，并分析基因突变与临床特征间的关系。 结果 108例MPN患者中，100例（92.59％）检出32种基因共211个突变，人均检出（1.96±1.32）个突变。85.19％（92/108）的患者检出驱动基因（JAK2、CALR、MPL）突变，其中69.56％（64/92）的患者至少检出1种附加基因突变。按突变频率由高到低依次为激活信号通路基因（42.2％，89/211）、DNA甲基化基因（17.6％，36/211）、染色质修饰基因（16.1％，34/211）。PV、ET、PMF三组间激活信号通路基因、表观遗传调节基因、剪接体和RNA代谢基因突变个数差异均有统计学意义，PMF附加基因平均突变数目高于ET及PV患者（1.69±1.39、0.67±0.70、0.87±1.22，χ2＝13.445，P＝0.001）。检出≥3个突变基因患者MPN总症状评估量表（MPN 10评分）（P＝0.006）、骨髓纤维化程度（P＝0.015）均较检出

Amyloid precursor protein (APP) is a highly conserved integral membrane protein extensively expressed in various types of cells. Previously we found that overexpression of APP in patients with AML1/ETO-positive acute myeloid leukemia (AML) associated with a higher incidence of extramedullary infiltrationin and indicate a poor prognosis. In this study, we attempted to define the roles of APP in AML1/ETO-positive leukemia cells. Western blotting and qRT-PCR analysis showed that protein levels of APP are significantly higher in Kasumi-1, a t(8;21)/ AML1/ETO-positive M2-type AML cell line. Stable knockdown of APP by lentivirus-based RNA interference (RNAi) dramatically impaired colony-formation and migration ability of Kasumi-1 cells, whereas APP knockdown had very little effect on cell viability, apoptosis, cell cycle and differentiation. We further explored whether the pan-histone deacetylase inhibitor panobinostat could deplete the protein levels of APP in Kasumi-1 cells. Treatment with panobinostat caused depletion of APP in Kasumi-1 cells. These findings indicate that overexpression of APP is involved in promoting proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat, which provide an attractive prospect for treatment of AML1/ETO-positive AML.

目的 探讨p16基因缺失在成人Ph染色体阳性急性淋巴细胞白血病（Ph+ ALL）中的临床意义。 方法 回顾性分析80例Ph+ALL伴p16基因缺失患者的临床特征、免疫表型、细胞遗传学、分子生物学改变及其预后。 结果 31.3% Ph+ALL患者合并p16基因缺失；p16基因缺失组与非缺失组相比，初诊时高白细胞计数（WBC≥30×109/L）更常见，高表达CD20，更易出现附加染色体异常，其中以累及7、8、19号染色体以及der（22）较为常见；两组诱导缓解率比较差异无统计学意义（P=0.033），p16基因缺失组患者治疗3个疗程后获BCR-ABL融合基因主要分子学反应（MMR）率和完全分子学反应（CMR）率均明显低于非缺失组（P值分别为0.034和0.036），且复发率明显高于非缺失组（P=0.033）；p16基因缺失组使用伊马替尼联合化疗者和使用达沙替尼联合化疗者的MMR、CMR率及复发率差异均无统计学意义（P值均>0.05）；p16基因缺失组患者3年总体生存（OS）率及无病生存（DFS）率分别为37.1%和12.4%，显著低于非缺失组的54.1%和45.9%（P值分别为0.037和0.026）；25例p16基因缺失患者中14例行异基因造血干细胞移植（allo-HSCT），其中位OS时间为21个月，明显长于非移植组患者的12个月（P=0.030）。 结论 成人Ph+ALL伴p16基因缺失患者预后相对较差，二代酪氨酸激酶抑制剂不能明显改善其疗效，但allo-HSCT能够改善部分患者的生存，明确p16基因缺失状态对于评估预后和指导临床治疗有重要意义。

The work investigated the influence of acetic acid (HAc) on the corrosion behavior of carbon steel exposed to the simulant solution. The analysis methods such as scanning electron microscopy, x-ray diffraction, energy dispersive spectroscopy, and x-ray photoelectron spectroscopy were employed to systematically characterize the morphology and component of the corrosion film. The corrosion rate was calculated by weight loss and electrochemical methods. In addition, the corrosion behavior was further studied by using potentiodynamic polarization and electrochemical impedance spectroscopy. It was shown that the corrosion potential and current density increased with increasing the amounts of HAc. The HAc concentration has an important effect on the corrosion film and the corrosion mechanism.