早幼粒细胞白血病蛋白及其细胞调控机制研究进展

早幼粒细胞白血病(PML)蛋白能调控细胞的多种生物学行为。现综述近年来PML蛋白在细胞中的作用及其作用机制的研究进展。     

早幼粒细胞白血病蛋白及其细胞调控机制研究进展

早幼粒细胞白血病（PML）蛋白能调控细胞的多种生物学行为。现综述近年来PML蛋白在细胞中的作用及其作用机制的研究进展。     

急性早幼粒细胞白血病诱导分化的分子机制研究进展

急性早幼粒细胞白血病(APL)以异常的早幼粒细胞无限增殖伴分化受阻为特点,95%以上的患者具有t(15;17)染色体异常,形成PML/RARα融合基因,被认为与APL的发病有关.自全反式维甲酸(ATRA)成功用于临床诱导APL分化以来,对诱导分化剂作用机制的研究已取得很大的进展.全文主要从细胞内蛋白激酶C、环-磷酸腺苷/蛋白激酶A信号途径、维甲酸受体、融合蛋白、核体、端粒酶、细胞周期与癌基因等方面对APL诱导分化的分子机制研究进展进行综述.     

亚砷酸治疗急性早幼粒细胞白血病的研究进展

急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)作为急性髓系白血病（acute myeloid leukemia,AML）的独特亚型,以异常的早幼粒细胞增多、危及生命的出血和t(15;17)染色体易位为特征,曾被认为是最凶险的白血病。亚砷酸（application of arsenite acid,ATO）的应用大大提高了该病的治疗效果,显著改善了患者的预后,大量患者长期生存。本文综述相关研究发现:ATO在肝脏中由无机砷（iSA）转化为甲基化砷,通过多种分子机制促进早幼粒细胞分化、凋亡。在任何年龄阶段,无论白细胞是否＞10×109/L,ATO联合其他药物治疗APL,都可以减少化疗药物的剂量,降低患者的累积复发率（CIR）,减少患者的死亡率。单药ATO可高效安全治疗APL。对于复发APL,一部分相关研究支持继续ATO+维甲酸（ATO+retinoic acid,ATRA）或ATO+ATRA+化疗的治疗,一部分研究支持移植前给予ATO治疗可显著改善患者的整体预后和长期生存,观点尚未统一,有待进一步研究。ATO常见的毒副作用主要为分化综合征（differentiation syndrome,DS）、心脏毒性及肝毒性,明显比化疗药物造成的毒副作用轻微。     

CD56和急性早幼粒细胞白血病相关研究进展

急性早幼粒细胞白血病（APL）是急性髓细胞白血病（AML）FAB分型中最有希望治愈的亚型，有其独特的生物学和临床特点。最近研究发现了一种CD56^＋的免疫亚型，其表达与临床预后不良有关。本文综述了CD56^＋的APL的特点及其与治疗相关的特点，以更好地进行APL分型，判断预后，提高CR率，降低复发和提高生存率。     

急性早幼粒细胞白血病治疗的进展

 自从应用全反式维A酸（ATRA）和砷剂（ATO）治疗急性早幼粒细胞白血病（APL）以来,APL疗效有了显著提高。初治与复发APL的完全缓解率达80 % ~ 90 %。对APL病理特征的分子遗传学认识的提高为治疗干预提供了理论的基础。近年来为延长无病生存期（DFS）进行了大量的研究,特别在APL新治疗方案和靶向治疗的策略以及新制剂方面的研究,取得良好的结果。     

急性早幼粒细胞性白血病的凋亡治疗研究进展

细胞凋亡，又称程序性细胞死亡，是在DNA损伤不能得到修复时细胞死亡的主要调节机制。凋亡作为正常细胞生长的一个组成部分，在调控细胞数量和增殖方面起重要的作用。急性早幼粒细胞性白血病（Acute promyelocytic leukemia，APL）是急性非淋巴细胞性白血病中的一个特殊亚型，约占10％～20％。白血病细胞有其特有的染色体异常t（15；17）（q22～23；q12—21），见于约90％以上的APL患者，尚未在其他ANLL中发现。     

有关急性早幼粒细胞白血病的一些问题

急性早幼粒细胞白血病(APL)约占成人急性髓系白血病(AML)中10%,以全反式维甲酸(ATRA)和蒽环类(柔红霉素、去甲氧柔红霉素、阿霉素、吡喃阿霉素等)联合化疗治疗,90%左右可完全缓解(CR).但仍有30%左右在4年～5年内复发.复发后用亚砷酸(三氧化二砷,As2O3)治疗,约80%还能再次CR.     

急性早幼粒细胞白血病耐药机制的研究进展

全反式维甲酸(ATRA)与三氧化二砷(As2O3)作为一线药物治疗急性早幼粒细胞白血病(APL)以来,APL患者的治愈率得到显著提高.但ATRA和(或)As2O3耐药的出现成为一个严重问题.现就近年来新提出的一些耐药机制如融合基因突变、细胞信号通路异常、染色质重构复合物异常、凋亡调控异常、骨髓微环境介导耐药等方面进行综述.     

Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body.

Telomerase-negative immortalized human cells maintain their telomeres by a mechanism known as alternative lengthening of telomeres (ALT). We report here that ALT cells contain a novel promyelocytic leukemia (PML) body (ALT-associated PML body, APB). APBs are large donut-shaped nuclear structures containing PML protein, telomeric DNA, and the telomere binding proteins human telomere repeat binding factors 1 and 2. Immunostaining showed that APBs also contain replication factor A, RAD51, and RAD52, proteins involved in DNA synthesis and recombination. During immortalization, APBs appeared at exactly the same time as activation of ALT. APBs were found in ALT tumors and cell lines but not in mortal cell strains or in telomerase-positive cell lines or tumors.     

Diagnostic utility of dual fusion PML/RARalpha translocation DNA probe (D-FISH) in acute promyelocytic leukemia

Translocation(15;17) leading to the formation of fusion gene PML/RARalpha is the diagnostic hallmark of acute promyelocytic leukemia (APL). Interphase fluorescence in situ hybridization (FISH) is one of the diagnostic tools employed for the detection of PML/RARalpha rearrangement. Using a dual color dual fusion (D-FISH) PML/RARalpha translocation DNA probe which hybridises both to PML/RARalpha and RARalpha/PML fusion genes, we characterised the FISH pattern of 52 APL patients at diagnosis and correlated the findings with conventional cytogenetics and RT-PCR analysis. The diagnostic sensitivity of the probe for PML/RARalpha was 100%. Seven patients had atypical D-FISH patterns; two had a masked PML/RARalpha fusion signal caused by the insertion of PML into RARalpha on 17q; 3 had an extra copy of PML/RARalpha in the form of isochromosome der(17)(q10)t(15;17) and one had duplication of the normal RARalpha gene with an ider(17q) masquerading as i(17)(q10). There was also one case of t(7;17;15) with a typical D-FISH pattern and in which metaphase FISH suggested an unusual 4-point break. In summary, PML/RARalpha D-FISH is a highly sensitive method for confirming diagnosis of APL. However D-FISH cannot be solely relied on for the diagnosis of APL owing to atypical patterns which are infrequently observed in cases with additional 17q structural abnormalities, gene insertion and gene duplication.     

Acute promyelocytic leukemia: PML/RARalpha and the leukemic stem cell.

Acute promyelocytic leukemia (APL) is distinguished from other acute myeloid leukemias (AMLs) by cytogenetic, clinical, as well as biological characteristics. The hallmark of APL is the t(15;17), which leads to the expression of the PML/RARalpha fusion protein. PML/RARalpha is the central leukemia-inducing lesion in APL and is directly targeted by all trans retinoic acid (t-RA) as well as by arsenic, both compounds able to induce complete remissions. This review focuses on potential stem cell involvement in APL outlining the knowledge about the APL-initiating stem cell and the influence of PML/RARalpha on the biology of the hematopoietic stem cell. Moreover, the importance of the blockage of t-RA signaling by the PML/RARalpha for the pathogenesis of APL is discussed, taking the relevance of the t-RA signaling pathway for the global hematopoiesis into account.