自噬在急性早幼粒细胞白血病中的研究进展

急性早幼粒细胞白血病（APL）具有特征性的t（15;17）（q22;q21）染色体易位,其表达PML-RARα融合蛋白。全反式维甲酸（ATRA）和三氧化二砷（As2O3）诱导早幼粒白血病细胞分化或凋亡,使APL成为第一种可以治愈的白血病。自噬是维持细胞稳态的重要代谢方式之一,最近有研究显示自噬在ATRA／As2O3诱导治疗中发挥重要作用,而且还可能影响APL对药物诱导凋亡作用的敏感性。因此,今后靶向自噬、调控自噬可能成为APL乃至于其他白血病治疗的一种新手段。对近年来自噬对APL的作用研究进行综述。     

慢性粒细胞白血病靶向治疗和靶向鸡尾酒疗法研究进展

酪氨酸激酶抑制剂（TKI）的应用显著改善了慢性粒细胞白血病（CML）患者的预后,但目前单用 TKI 仍难以根治 CML。除更有效 TKI 类药物的研发及现有药物的精确使用外,CML 其他分子靶点的开发、针对 CML 肿瘤干细胞的治疗研究和联合用药为改进治疗和治愈 CML 带来新的希望。文章就相关研究进展进行综述。     

BCR-ABL持续表达在慢性粒细胞白血病急性变中的作用

BCR-ABL持续表达可影响慢性粒细胞白血病细胞的生物学改变,促进白血病细胞的增殖、抑制细胞凋亡、阻断细胞分化、导致p53基因功能失活、c-myc基因表达增加及引起其他继发性染色体改变。该文就近年来BCR-ABL持续表达在慢性粒细胞白血病急性变中的作用的研究进展作一综述。     

自噬与急性白血病治疗

自噬在急性白血病发生、发展中具有重要的双重作用:一方面可以诱导白血病细胞的凋亡,抑制疾病发展,另一方面可以对白血病细胞产生保护作用而维持细胞生存,以及抵抗化疗药物诱导的凋亡。目前已有研究发现通过调控自噬可增强急性白血病细胞的药物敏感性,促进白血病细胞死亡。因此,通过调控自噬有望为难治复发急性白血病找到更为有效的治疗措施。文章对近年来自噬与急性白血病治疗相关研究进展进行综述。     

高三尖杉酯碱治疗慢性粒细胞白血病

 　目的　研究高三尖杉酯碱（HHT）治疗慢性粒细胞白血病（CML）的疗效及安全性。方法　12例初诊CML患者,HHT 2.5 mg·m-2·d-1,静脉滴注维持6 h以上,持续14 ~ 21 d为 1个疗程。有效者每月HHT维持治疗,并以外周血中性粒细胞绝对值≥1.0×109／L、血小板≥40×109／L调整用药时间,一般用药5～14 d。每3个月或3个疗程后复查染色体。6个月后以羟基脲（Hu）维持治疗。结果　12例患者中,7例（58.3 %）获血液学完全缓解（CHR）,3个疗程后,总的细胞遗传学反应率50 %（3例CCR,3例MCR）;另5例（41.7 %）在治疗3个月内进入加速期或急变期（4例发生在HHT 1个疗程后）。12例患者中有6例出现严重骨髓抑制,均发生于CHR者。结论　HHT治疗CML-CP,可获得较高的血液学和细胞遗传学缓解率,但也可能早期进入加速期或急变期。     

慢性粒细胞白血病尺骨髓外急性淋巴细胞变一例

患者男,42岁.因确诊为慢性粒细胞白血病(CML)6月余,左肘关节疼痛3周于2005年10月6日收入我院血液科.6个月前因乏力,左上腹部饱胀不适,脾大,WBC 113.65×109/L,N 0.85,Hb 117 g/L,Plt 111×109/L就诊,骨髓穿刺示骨髓有核细胞增生明显活跃,粒:红=43.5:1,原粒及早幼粒0.003,中性中、晚幼粒及杆状核粒细胞比例明显增高,嗜碱性粒细胞0.005,ALP染色6%、积分6分,骨髓活检:增生极度活跃,粒系明显增生,以成熟阶段粒细胞增生为主,巨核细胞可见,红系淋巴细胞减少.RT-PCR检测bcr-abl融合基因:1.67×104拷贝/2μgRNA,Ph染色体阳性.诊断:CML慢性期.     

慢性粒细胞白血病靶向治疗研究进展

酪氨酸激酶抑制剂（TKI）的应用革命性地改善了慢性粒细胞白血病（CML）患者的治疗结果和生存。当前治疗CML的新目标是如何获得持续的深度分子生物学反应,以减少耐药复发,甚至实现无治疗的缓解维持和治愈。国际上已有4种TKI获批用于一线治疗初诊的慢性期CML,并且不断有新的药物和治疗方案在研发和临床研究中。文章结合第62届美国血液学会年会相关报道介绍CML靶向治疗研究进展。     

STI571治疗慢性粒细胞白血病相关策略

慢性髓细胞白血病 (CML)是一类造血干细胞克隆增殖紊乱性疾病 ,预后较差 ,蛋白酪氨酸激酶抑制剂STI5 71的出现使其治疗出现转机 ,其能阻断Bcr Abl蛋白激酶的活性 ,选择性抑制白血病细胞增殖。但随着临床应用的深入 ,常出现对STI5 71耐药及治疗后复发病例。因此针对耐药和复发的机制及相关治疗策略的研究也在不断深入 ,现综述STI5 71治疗策略的研究进展。     

STI571治疗慢性粒细胞白血病相关策略

慢性髓细胞白血病(CML)是一类造血干细胞克隆增殖紊乱性疾病,预后较差,蛋白酪氨酸激酶抑制剂STI571的出现使其治疗出现转机,其能阻断Bcr-Abl蛋白激酶的活性,选择性抑制白血病细胞增殖.但随着临床应用的深入,常出现对STI571耐药及治疗后复发病例.因此针对耐药和复发的机制及相关治疗策略的研究也在不断深入,现综述STI571治疗策略的研究进展.     

亚砷酸注射液治疗慢性粒细胞白血病疗效分析

为了评估亚砷酸注射液治疗成人慢性粒细胞性白血病（CML）的疗效,对温州医学院附属第三医院2002年1月～2005年12月住院的成人慢性粒细胞性白血病患者26例,采用亚砷酸注射液进行治疗,10mL/d,加入5%葡萄糖溶液500mL内缓慢静滴,用药时间28～35d。其中初治14例,难治或复发12例。26例患者中,完全缓解（CR）14例（53.9%）,部分缓解（PR）8例（30.7%）,无效（NR）4例（15.4%）,总缓解率（有效率）为84.6%。由此可见,亚砷酸注射液为治疗慢性粒细胞白血病一种有效药物,且毒副反应较轻,患者可耐受。     

Progress in the treatment of acute myelogenous leukemia

Results of treatment of AML have substantially progressed within the last decade. In almost all cases, the AML 3-year-survival rate did not exceed 1% in the 1960s. The 5-year disease-free survival rate now is ranges from 10% to 25% in adults and up to 45% in children. The 3-year survival at our hospital is 50%. Recent chemotherapy for acute leukemia is aimed at not only remission induction but also cure of the disease. Although some hematologists claim to stop chemotherapy as early as possible, there is considerable controversy regarding the total length of postremission treatment. Bone marrow transplantation is increasingly used to treat patients with acute leukemia in many facilities. Bone marrow transplantation assures a lower relapse rate than with chemotherapy alone. The limitations are the risk of transplant-related mortality, lack of a histo-compatible donor and advanced age. To achieve substantial improvement in results of AML treatment requires the development of new drugs, and the reduction of transplant-related death. An attempt to establish registries of HLA type for the transplantation from unrelated, HLA-identical donors is now under way.     

Current treatment approaches for chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder that progresses through distinct phases characterized by progressive loss of the differentiation of the malignant clone. Over the past 4 decades, it has been established that the Bcr-Abl protein, created as a consequence of a (9:22) chromosomal translocation, is the cause of the disease. Bcr-Abl functions as a constitutively activated tyrosine kinase, and this kinase activity is absolutely required for the transforming function of the Bcr-Abl protein. Thus, a specific inhibitor of the Bcr-Abl tyrosine kinase would be predicted to be an effective and selective therapeutic agent for CML. STI571, an Abl-specific tyrosine kinase inhibitor, has shown remarkable activity in all phases of CML. The clinical features, molecular pathogenesis, and current treatment options of CML are reviewed along with the development of STI571, the phase I clinical results, and the application of this paradigm to other malignancies.     

The biology and treatment of chronic myelogenous leukemia

Over the past 2 decades, our understanding of the pathobiological events underlying chronic myelogenous leukemia (CML) has grown. At the same time, effective transplant and nontransplant treatment approaches to CML have been developed that increase the options available to newly diagnosed patients, and that can cure or prolong survival in this formerly incurable disease. Newly diagnosed patients presenting with extreme leukocytosis or thrombocytosis may benefit from immediate therapy with hydroxyurea (Hydrea) and pheresis. After stabilization, eligible patients may elect to undergo immediate transplant. The majority, however, should begin therapy with either interferon-alpha and cytarabine, or they should be entered into the STI-571 trials.     

Immunotherapy in chronic myelogenous leukemia

Chronic myelogenous leukemia is one of the leukemic disorders more responsive to immunotherapy. Interferon-based regimens were the first treatment to produce complete cytogenetic responses, and this agent has been classified as an immunotherapeutic agent. Although most patients are now treated with imatinib as first-line therapy, a combination of interferon and imatinib could increase the rate of molecular responses and prevent patients from experiencing relapse. Thus, large phase III trials are currently exploring this strategy. Allogeneic stem cell transplantation also involves the immune system, with fewer patients in relapse in case they experience graft-versushost disease. Vaccine strategies are also promising with phase II ongoing trials. These vaccine strategies include the use of oligopeptides derived from the Bcr-Abl junction. Initial results indicate a good safety profile of these therapies in patients exhibiting complete cytogenetic response and molecular responses. These 3 different approaches of immunotherapy are described herein. Although these results obtained with imatinib are promising, this tyrosine kinase inhibitor does not eradicate leukemic stem cells. Thus, immunotherapeutic strategies are still being investigated in chronic myelogenous leukemia.     

甲磺酸伊马替尼治疗慢性粒细胞白血病的临床观察

目的:总结甲磺酸伊马替尼(IM)治疗Ph阳性慢性粒细胞白血病(CML)患者的临床观察体会。方法:收集110例Ph阳性CML慢性期(CP)患者、6例加速期(AP)患者和4例急变期(BC)患者分别口服IM 400、600或800 mg/d。通过血液学、细胞遗传学和分子遗传学指标来判断疗效。结果:CP患者完全血液学反应(CHR)率、主要细胞遗传学反应(MCyR)率和完全细胞遗传学反应(CCyR)率分别为98.2%、90.9%和80.9%;AP分别为66.7%、33.3%和16.7%,P值分别为0.002、0.000和0.000。其中CP患者中肝肾功能不全的患者需减少IM剂量。27例经干扰素治疗失败的CP患者IM治疗仍有效。第1年高随访(1次/月)CP患者CCyR达81.9%,非高随访则为63.6%,P=0.005 2。服药前肾功能不全和肝功能不全较脏器功能正常的CP患者服药6个月内发生3~4级血液学毒副反应概率增高,服药6个月后有所减少。结论:IM对CP患者包括干扰素治疗失败的有较高疗效,对AP和BC患者有一定近期疗效。肝肾功能不全的患者易出现血液学毒副反应,需要药物剂量调整。     

Leukocyte interferon in the treatment of chronic myelogenous leukemia in second chronic phase

Four patients with Philadelphia chromosome positive CML were treated with 18-42 x 10(6) IU of purified natural leukocyte IFN-alpha per week, after high-dose chemotherapy for blast phase and attainment of 2nd chronic phase. The second blast phase occurred within 3 months in 3 patients, but one patient is still in second chronic phase after 22 months of treatment. Treatment consisted of interferon only during the first year, and interferon in combination with hydroxyurea during the second year. During the second year suppression of the Philadelphia chromosome was seen in one patient, with 20% Philadelphia negative bone marrow metaphases. The toxicity of purified natural leukocyte IFN-alpha was similar to the toxicity of recombinant IFN-alpha. Antibodies to IFN-alpha were not detected in any patient.     

Coexistence of chronic myelogenous leukemia and chronic lymphocytic leukemia

A 55-year-old man is reported who initially developed chronic lymphocytic leukemia. Seven years later, after chemotherapy with chlorambucil, chronic myelogenous leukemia was diagnosed in addition to the chronic lymphocytic leukemia. Four previously reported cases with the same sequence of events are reviewed as well as cases of chronic myelogenous leukemia following chemotherapy alone.