混合表型急性白血病的细胞及分子遗传学研究进展

混合表型急性白血病(mixed-phenotype acute leukemia, MPAL)是一类同时表达不止一个谱系特异性抗原的恶性克隆性疾病,发生率低,仅占急性白血病的2%~5%。多数MPAL患者可检测出克隆性染色体异常及分子遗传学改变,其中一些特异性异常如t(9;22)(q34;q11)及KMT2A重排在MPAL的诊断分型、靶向治疗及预后判断中具有重要的指导意义。近年来,随着全基因组测序、全外显子测序、靶向测序及单核苷酸多态性-微阵列比较基因组杂交等分子生物学技术的广泛应用,人们发现一些新的分子遗传学异常如ZNF384重排及WT1基因突变等也与疾病的发生发展及预后密切相关。这些发现进一步丰富了对MPAL发病机制的认识。现将有关MPAL细胞及分子遗传学的研究进展进行综述。     

The Influence of Morphology on Prognosis in Acute Leukemia

The presence of definite cytoplasmic granulation in at least some of the malignant cells was used as the sole criterion to separate 156 patients with acute leukemia into two groups: 110 with myeloblastic (AML), and 46 with lymphoblastic or stem cell leukemia (ALL). The median survival from the onset of symptoms in patients with AML was 20 weeks, and those with ALL 37 weeks. The difference in survival in these two groups is much greater for patients under the age of 25 than for those over the age of 25.     

自噬与急性早幼粒细胞白血病

急性早幼粒细胞白血病(APL)是急性髓性白血病的一种亚型,其分子特征是具有t(15;17)(q22;q21)染色体易位,并形成融合肿瘤蛋白,进而阻止早幼粒细胞分化成熟。全反式维甲酸(ATRA)和三氧化二砷(ATO)作为经典的治疗APL的药物,能够通过转录调节并激活泛素-蛋白酶体通路,促进融合肿瘤蛋白降解,发挥其临床抗白血病的功效。最近的研究发现,ATRA与ATO均能够诱导APL细胞自噬,且自噬在融合肿瘤蛋白降解及诱导早幼粒细胞分化中发挥至关重要的作用。我们简要综述近年来APL的研究进展及自噬在APL治疗中的作用。     

Platelet Changes in Acute Leukemia

Acute leukemia is a hematopoietic stem cell malignant disease, with abnormal proliferation of leukemic and immature cells that suppress the production of normal blood cells and extensively invade peripheral tissues. The bleeding complications are very common in acute leukemia and often lead to death. One major cause for hemorrhage is thrombocytopenia, which is caused by the replacement of normal bone marrow cells with leukemic cells and the inhibition of megakaryocytes functions. Declines in platelet count as well as in function in acute leukemia have been reported in many studies. Here, we reviewed the literatures concerning platelet changes in acute leukemia.     

急性单核细胞白血病M5转为急性红白血病M6一例病例分析及文献复习

目的:红白血病为临床少见的急性髓系白血病亚型,白血病克隆转换不常见,在国内外文献中有关报道少见.通过对一例由急性单核细胞白血病转化的急性红白血病(acute erythroid leukemias,AEL)的病例分析,学习并探讨急性红白血病的临床特点及实验室检查特征,提高对急性红白血病疾病特点及白血病克隆转化的认识.方法:报道一例初诊为急性单核细胞白血病,后转为急性红白血病的患者.期间对其进行持续的细胞形态学,遗传学及分子生物学监测.结果:患者首次入院诊断为急性单核细胞白血病,经过一个疗程化疗后,骨穿显示从急性单核细胞白血病转为急性红白血病.随后再进行了一个疗程化疗,化疗结束后患者好转出院.后因经济原因,患者未继续治疗,2月后随访,患者死亡.结论:本例急性单核细胞性白血病化疗后转为红白血病.究其机制,可能有:一.发病是粒-单定向祖细胞和红系定向祖细胞同时受损,只是早期单核细胞系异常表现明显,红系异常早期表现不明显.或疾病起源于更早期造血干细胞,导致单核系和红系均有异常.二.在疾病过程中,骨髓微环境的变化,诱导红系异常而导致红白血病的发生.经过分析,本病例中,疾病可能起源于更早期造血干细胞的可能性较大,而骨髓微环境在疾病变化过程中则起到了重要的作用.这一结果有待进一步临床观察研究和肯定.提醒临床医生,提高动态的诊断和治疗意识,将有助于该疾病的预防、诊断和治疗.     

成人急性髓性白血病SOCS-1 基因及其甲基化的研究

目的:通过检测成人急性髓性白血病中SOCS-1基因表达水平及其甲基化水平,研究其在白血病发病中的作用。方法:运用甲基化特异性PCR(Methylation specific PCR,MSP)方法,对24例急性髓性白血病患者和4株白血病细胞株(Jurkat、Raji、U 937、NALM 17),进行SOCS-1基因甲基化水平的研究;同时运用Real-time PCR法定量分析SOCS-1基因表达水平。以10例健康人为正常对照组。结果:24例成人急性髓性白血病患者中,15例有SOCS-1基因甲基化(62.5%),而正常对照组无SOCS-1基因甲基化(0%),二者有显著差异(P<0.05);SOCS-1基因甲基化组与无SOCS-1基因甲基化组相比较,其SOCS-1基因相对表达量明显减少(P﹤0.05);与患者临床病理特征相结合比较,发现SOCS-1基因的甲基化与患者年龄、性别和病程阶段无相关。4株白血病细胞株中,Jurkat和U 937表现有SOCS-1甲基化(50%),Raji和NALM 17无SOCS-1甲基化,前者SOCS-1基因表达量较后者也明显降低(P<0.05)。结论:SOCS-1基因在成人急性髓性白血病中甲基化水平明显增高,且SOCS-1基因甲基化后表达水平受到抑制,提示SOCS-1基因及其甲基化在急性髓性白血病的发生发展中可能具有一定作用。     

成人急性髓性白血病SOCS-1基因及其甲基化的研究

目的：通过检测成人急性髓性白血病中SOCS．1基因表达水平及其甲基化水平,研究其在白血病发病中的作用。方法：运用甲基化特异性PCR（Methylation specificPCR,MSP）方法,对24例急性髓性白血病患者和4株白血病细胞株（Jurkat、Raji、U937、NALM17）,进行SOCS-1基因甲基化水平的研究;同时运用Real—timePCR法定量分析SOCS—1基因表达水平。以10例健康人为正常对照组。结果：24例成人急性髓性白血病患者中,15例有SOCS-1基因甲基化（62．5％）,而正常对照组无SOCS-1基因甲基化（0％）,二者有显著差异（P〈0．05）;SOCS-1基因甲基化组与无SOCS-1基因甲基化组相比较,其SOCS—1基因相对表达量明显减少（P口0．05）;与患者临床病理特征相结合比较,发现SOCS-1基因的甲基化与患者年龄、性别和病程阶段无相关。4株白血病细胞株中,Jurkat和U937表现有SOCS—1甲基化（50％）,Raji和NALM17无SOCS—1甲基化,前者SOCS-1基因表达量较后者也明显降低（P〈0．05）。结论：SOCS—1基因在成人急性髓性白血病中甲基化水平明显增高,且SOCS-1基因甲基化后表达水平受到抑制,提示SOCS-1基因及其甲基化在急性髓性白血病的发生发展中可能具有一定作用。     

难治性急性白血病研究现状与进展

难治性急性白血病治疗反应差,诱导缓解率低,复发率高,生存期短,因而是白血病治疗中的难题。本文从难治性急性白血病诊断标准与免疫学、细胞遗传学及分子生物学特征,多药耐药与难治性白血病,难治性急性白血病治疗现状以及治疗展望五大方面阐述了难治性急性白血病研究现状与进展。基础与初步临床研究显示中药配合化疗能够提高难治性急性白血病围化疗期临床缓解率。认为中药在提高难治性白血病临床疗效方面具有潜在临床应用前景和开发的商业价值,值得进行深入研究。     

microRNA在急性淋巴细胞白血病中的作用

MicroRNAs(miRNAs)是一类非编码小RNA分子,其通过降解mRNAs或抑制mRNAs翻译来负调控基因表达并可能调控着几乎每一个细胞生理进程.急性淋巴细胞白血病(ALL)是儿童时期最常见的血液肿瘤,miRNA的异常表达谱对于ALL的发病机制与临床应用有至关重要的作用,因此miRNAs已迅速成为ALL潜在的治疗靶点.     

急性白血病化疗后心肌病的研究进展

目前临床上广泛用于急性白血病化疗的药物,常具有严重的毒副反应包括心肌毒性,其引起的充血性心力衰竭(congestive heart failure,CHF)已成为急性白血病患者化疗后的致死原因之一.因此在维持化疗药物治疗效果的同时,降低其心脏毒性,减少急性白血病化疗后心肌病是近年来的研究热点.关于这方面的研究进展主要包括监测技术的进展、高效低毒化疗药物的研究和应用进展以及心肌保护剂的进展.监测手段的研究进展使得对心肌损伤的监测更敏感、更便于操作.抗肿瘤药物衍生物的研究进展如去甲氧柔红霉素(idarubicin,IDA)、米托蒽醌(mitoxantrone,MTZ)及脂质体阿霉素(liposomal anthracyclines)等高效低毒药物在增强了其抗肿瘤活性的同时,明显降低了其心肌毒性,减少了心肌病的发生率.另外制定化疗方案前应充分评估患者高危因素,限制累积剂量的应用也明显降低了化疗药物的心肌毒性.心肌保护剂的应用也已成为防治急性白血病化疗后心肌病的有效手段,如右丙亚胺(Dexrazoxane,DEX)有明确的心肌保护作用,研究表明DEX的使用并不影响抗肿瘤药物原有的抗肿瘤活性,有广泛的临床应用价值.     

Remission Maintenance Therapy in Acute Myelogenous Leukemia

Because no conclusive evidence as to the efficacy of maintenance chemotherapy in acute myelogenous leukemia (AML) existed, a study to obtain such information was done. Twenty-six adult patients with AML in whom complete remission had been achieved following induction chemotherapy were randomly assigned to receive either maintenance chemotherapy consisting of cytarabine and 6-thioguanine for two days each month or to receive no maintenance therapy. The data showed a significant difference in remission duration between the two groups, with median remission lengths for the maintained and unmaintained groups being 10.3 and 6.7 months, respectively (p<.05). In 46 percent of the maintained patients there were remissions lasting longer than 11 months, whereas in none of the unmaintained patients was there such a prolonged remission. No significant drug-induced toxicity was observed. That the prolonged exposure to these chemotherapeutic agents, which were also used in our induction program, did not adversely affect the rate of successful reinduction therapy was shown by identical 50 percent complete remission rates for second inductions in both groups. In patients with palpable splenomegaly at the time of diagnosis, there was no prolongation of remission with maintenance therapy. These data indicate the potential utility of maintenance chemotherapy for prolonging remission duration in acute myelogenous leukemia.     

Radiotherapy in the Management of Leukemia

Localized radiation therapy directed to the spleen and other sites, supplemented by a whole-body radiation technique, appeared to increase survival time in the chronic leukemias. In recent years the alkylating drugs have provided a more convenient form of “whole-body effect”, because treatment can be taken at home and yet observation maintained.Small or medium field radiation therapy remains the most efficient means of controlling localized leukemic infiltrations. Splenic irradiation has been used successfully in the control of hemolytic anemia occurring during the course of chronic leukemia where steroids have failed.Proper management of the leukemias requires close co-operation between the radiotherapist, internist and hematologist.