慢性中性粒细胞白血病

慢性中性粒细胞白血病(chronicneutrophilic leukemia,CNL)是一种少见类型的慢性白血病,临床上以成熟中性粒细胞持续增多,脾大为主要特征,1920年首先由Tuohy描述,以后国内外陆续有病例报道,有作者认为本病是慢性髓细胞白血病(CML)的一个亚型,1966年Rubin称之为CNL,随后的报道均沿用这一名称.     

慢性粒细胞白血病相关抗原HLA-A2.1限制性CTL表位的生物信息学分析

目的:预测慢性粒细胞白血病BCR/ABL融合基因HLA-A2.1限制性细胞毒性T细胞表位.方法:运用BIMAS、SYFPEITHI、Predep、Immune Epitope Database和Analysis Resource(IEDB)软件预测BCR/ABL融合基因可能的HLA-A2.1限制性CTL表位.结果:结合BIMAS、SYFPEITHI、Predep和IEDB预测BCR/ABL融合基因的HLA-A2.1限制性CTL表位,共6条.结论:综合运用多个预测软件可提高预测效率获得目的表位肽,为下一步基础实验打下基础.     

慢性中性粒细胞白血病4例临床分析

慢性中性粒细胞白血病（chronic neutrophilic leukemia,CNL）是一种少见的慢性白血病,临床上以成熟中性粒细胞持续增多、脾大为主要特征,目前尚无统一诊断标准,但近年WHO倾向于将其归类于慢性骨髓增殖性疾病,本文收集4例CNL进行分析如下。     

造血干细胞移植治疗慢性粒细胞白血病中监测BCR／ABL融合基因的应用

目的 研究应用筑巢式逆转录多聚合酶链反应法(nested．RT-PCR)监测bcr／abl融合基因mRNA在异基因造血干细胞移植治疗慢性粒细胞白血病(CML)效果监测方面的价值。方法 应用RT-PCR方法定期检测异基因造血干细胞移植治疗慢性粒细胞白血病患者前后bcr／abl融合基因表达情况。结果 异基因造血干细胞移植治疗组完全血液学缓解率为100％，分子生物学缓解率分别为87．5％。结论 bcr／abl融合基因监测可以作为CML评价疗效的指标，适用于微小残留病变的监测。     

慢性粒细胞白血病临床和实验研究：附60例报告

初步探讨慢性粒细胞白血病的分期,和治疗,方法分析了６０例患进的临床资料并用Ｒ显带技术检查了４９例患者的染色体核型,用逆转录－聚合链反应法检查了１３例,ＢＣＲ－ＡＢＬ融合基因。     

慢性中性粒细胞白血病2例并文献复习

目的:研究对慢性中性粒细胞白血病(CNL)的特点.方法:报告2例CNL并结合文献进行复习.结果:患者中性粒细胞明显增多,脾大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体、bcr-abl融合基因,骨髓粒系增生,无病态造血和明显纤维化依据,排除了如类白血病反应、其他克隆性血液病引起的中性粒细胞增多,其中1例伴有单克隆免疫球蛋白血症,2.5年后转化为急性白血病.结论:CNL是一种少见的骨髓增殖性疾病,多发生于老年人,预后差,治疗无标准方案,年轻患者应进行异基因造血干细胞移植以达到治愈目的.     

慢性中性粒细胞白血病2例并文献复习

目的：研究对慢性中性粒细胞白血病（CNL）的特点。方法：报告2例CNL并结合文献进行复习。结果;患者中性粒细胞明显增多,脾大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体、bcr-abl融合基因,骨髓粒系增生,无病态造血和明显纤维化依据,排除了如类白血病反应、其他克隆性血液病引起的中性粒细胞增多,其中1例伴有单克隆免疫球蛋白血症,2．5年后转化为急性白血病。结论;CNL是一种少见的骨髓增殖性疾病,多发生于老年人,预后差,治疗无标准方案,年轻患者应进行异基因造血干细胞移植以达到治愈目的。     

慢性粒细胞白血病伴戈谢细胞增多一例

患者男性,45岁,2004年7月21日因发现白细胞高18年就诊。患者18年前因皮肤感染迁延不愈,外院查血常规示白细胞高于40×109/L,血小板和红细胞具体数值不详,骨髓细胞检查示:骨髓有核细胞增生极度活跃,粒∶红=6.5∶1,粒细胞系占0.775,NAP:阴性,考虑为慢性粒细胞白血病(CML),给予白消安、靛玉红交替服用,白细胞控制在10×109/L以下。于1997年10月复查骨髓细胞示:骨髓有核细胞增生明显活跃,粒∶红=5.4∶1,粒系明显增生,占0.76,中幼粒比值明显增高,杆状核粒细胞胞体增大,其他细胞形态大致正常;红细胞系增生偏低,全片见巨核细胞7个,后改用羟基脲…     

慢性中性粒细胞白血病1例

患者男性,60岁,于2013年12月就诊于山东大学齐鲁医院,行右侧疝气修补术时发现脾肿大、白细胞升高,外周血白细胞波动在20×109/L左右,分叶核粒细胞约占85%,血小板和红细胞计数正常,未见幼稚细胞.2014年1月行骨髓穿刺检查:骨髓增生活跃,以粒系增生为主,无骨髓纤维化(图1~3), NAP积分为310分,阳性率92%.无Ph染色体,BCR-ABL1融合基因(-),JAK2-V617F突变(-),单克隆免疫球蛋白检查正常,全身CT扫描排除肿瘤和感染性疾病.初步诊断:骨髓增殖性疾病,未予治疗.2014年10月患者出现消化道出血,初步诊断为乙肝肝硬化、门脉高压、脾肿大,遂行脾脏切除+贲门胃底静脉离断术.术中见肝脏轻度结节性肝硬化表现,脾脏大小为20 cm×20 cm×15 cm.术后2 d患者出现高热、呼吸困难,白细胞升高至105×109/L,中性粒细胞占90%,血小板165× 109/L.考虑患者白细胞升高是术后感染和手术应激导致的类白血病反应,给予抗感染和支持治疗.     

适形结合调强放疗在胸中段食管癌中对正常组织受量的影响

目的:比较适形结合调强放疗与单纯调强放疗在胸中段食管癌放疗中的正常组织剂量分布情况,为临床食管癌放疗计划的选择提供参考。方法:选择36例胸中段食管癌患者进行CT定位扫描。由主治及以上医师勾画出放疗靶区,设计两组放疗方案。A组为调强与适形放疗相结合的方式(其中适形放疗10次,调强放疗20次);B组为单纯的调强放疗(30次)。最后以95%PTV体积获得60Gy处方剂量进行剂量归一,利用剂量体积直方图(DVH)对以上两组计划进行下列参数的比较。两侧肺分别受量为5Gy、10Gy、15Gy、20Gy、25Gy、30Gy、35Gy、40Gy、50Gy及肺部平均受量Vlung时的体积值;心脏受量为20Gy、30Gy、40Gy、50Gy及心脏平均受量Vheart时的体积值;脊髓最大点受量。结果:A组肺部除V40及V50外,其余各组数据均较B组降低。A组心脏受量仅V40及V50较B组增加,显示有统计学差异(P≤0.007)。A组脊髓最大点受量较B组增加(P<0.05)。结论:食管癌的放疗计划中,使用调强与适形结合的方式,可以在基本不增加心脏和脊髓受量的同时有效减少肺低剂量区受照射体积。     

BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment.Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusionprotein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the fivecandidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations (IC50) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes ofapoptosis such as shrunken, fragmentation nucleus as well as “apoptotic bodies” after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.     

Expanding Nilotinib Access in Clinical Trials (ENACT): an open-label, multicenter study of oral nilotinib in adult patients with imatinib-resistant or imatinib-intolerant Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase

BACKGROUND:

Nilotinib is a selective, potent BCR‐ABL inhibitor. Previous studies demonstrated the efficacy and safety of nilotinib in Philadelphia chromosome‐positive chronic myeloid leukemia patients in chronic phase (CML‐CP) or accelerated phase who failed prior imatinib.

METHODS:

This expanded access trial further characterized the safety of nilotinib 400 mg twice daily in patients with CML‐CP (N = 1422).

RESULTS:

In this large, heavily pretreated population, nilotinib demonstrated significant efficacy, with complete hematologic response and complete cytogenetic response achieved in 43% and 34% of patients, respectively. Responses were rapid, mostly occurring within 6 months, and were higher in patients with suboptimal response to imatinib, with 75% and 50% achieving major cytogenetic response and complete cytogenetic response, respectively. At 18 months, the progression‐free survival rate was 80%. Most patients achieved planned dosing of 400 mg twice daily and maintained the dose >12 months. Nonhematologic adverse events (AEs) were mostly mild to moderate and included rash (28%), headache (25%), and nausea (17%). Grade 3 or 4 thrombocytopenia (22%), neutropenia (14%), and anemia (3%) were low and managed by dose reduction or brief interruption. Grade 3 or 4 elevations in serum bilirubin and lipase occurred in 4% and 7% of patients, respectively. The incidence of newly occurring AEs decreased over time. Of patients who experienced a dose reduction because of AEs and attempted a re‐escalation, 87% successfully achieved re‐escalation to the full dose.

CONCLUSIONS:

This large study confirms that nilotinib was well tolerated and that grade 3 or 4 AEs occurred infrequently and were manageable through transient dose interruptions. Cancer 2012;. © 2011 American Cancer Society.     

BCR／ABL基因对PTEN介导的信号通路在K562细胞增殖和凋亡中的影响

目的：探讨BCR／ABL融合基因对抑癌基因PTEN介导的信号传导通路在K562细胞增殖和凋亡中的影响。方法：用不同浓度的格列卫（0．5、1、2、5、10μg／ml）干预K562细胞不同时间,观察其对细胞增殖的影响。用1μg／ml浓度的格列卫干预K562细胞不同时间（12、24、36、48、72h）后,通过荧光定量PCR检测细胞BCR／ABL、PTEN、mTOR mRNA水平的变化,并分析它们之间的相互关系。Western blotting检测细胞Akt和p-Akt水平,分析BCR／ABL融合基因对HEN mRNA表达的影响。结果：1μg／ml格列卫作用K562细胞后随着BCR／ABL融合基因表达减低,PTEN mRNA表达上调,mTOR mRNA表达下调,p-Akt表达下调。48h后随着BCR／ABL融合基因的抑制减弱,PTEN mRNA表达进而减低,而mTOR mRNA表达升高,p-Akt持续降低。BCR／ABL mRNA表达与PTEN mRNA表达呈负相关（r=-0．881,P〈0．05）,与mTOR mRNA及p-Akt表达呈正相关（依次为r=0．961,r=0．879,P均〈0．05）。结论：BCR／ABL融合基因可以通过抑制PTEN基因表达,调控P13K／Akt、mTOR信号传导通路,参与细胞增殖、凋亡及细胞周期调控等生物学特性。     

IKZF1基因在BCR/ABL融合基因阳性急性淋巴细胞白血病中的表达及机制探讨

目的:探讨IKZF1基因在急性淋巴细胞白血病中的表达特点及可能机制,进一步明确急性淋巴细胞白血病的发病机理.方法:收取80例急性淋巴细胞白血病患者的外周血标本,其中21例BCR/ABL融合基因阳性,均为B细胞急性淋巴细胞白血病.RT-PCR技术检测IKZF1基因、RAG1基因及RAG2基因的表达;提取细胞DNA,PCR...