Acute lymphoblastic leukemia: introduction.
Acute lymphoblastic leukemia: introduction.
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DOI：
10.1053/j.seminhematol.2008.09.011
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发表时间：
2009-01
影响因子：
3.6
通讯作者：
Pui CH
中科院分区：
文献类型：
--
作者：
Pui CH
现代治疗急性淋巴细胞性白血病(ALL)可以治愈80%以上的儿童这种疾病，但不到50%的成年人。1目前的风险导向治疗不仅旨在提高总的治愈率，而且还旨在提高患者的生活质量，减少急性发病率和长期后遗症。2随着我们不断了解白血病细胞转化和耐药性产生的机制，以及种系基因对患者化疗反应的影响，我们越接近一个为所有人提供个性化治疗的时代，在这个时代，针对大量患者的共同方案将被基于个别患者独特的分子靶点和药效学的治疗方案所取代。3在本期血液学研讨会中，一组杰出的研究人员回顾了白血病病理生物学和治疗的当前和新兴概念，强调了如果我们希望在不产生可能妨碍正常生产生活的不适当副作用的情况下根除ALL必须解决的问题。白血病是由造血干细胞或其承诺的祖细胞的原癌基因、肿瘤抑制基因和microRNA基因的顺序变化引起的。3、4这些根本性的变化改变了靶细胞的关键调控过程，释放了自我更新的无限能力，颠覆了正常增殖的控制，阻止了细胞分化，并促进了对死亡信号的抵抗(细胞凋亡)。3、4尽管在对所有常见的分子损伤进行分类方面取得了显著的进展，但我们对这些变化如何协同产生公开的ALL的理解充其量仍然是初级的。Mullight an和Downing巧妙地讨论了使用高分辨率全基因组平台来检测DNA拷贝数异常和杂合性丢失区域的最新进展，从而解决了这个问题。结合转录图谱，这些研究可以用来确定肿瘤抑制基因和其他致癌病变之间的相互作用，这些不仅提供了有价值的机制见解，而且还可能成为有用的治疗靶点。5、6作者相当谨慎地强调了数据的一些技术方面
Contemporary treatments for acute lymphoblastic leukemia (ALL) can cure more than 80% of children with this disease but fewer than 50% of adults. 1 Current risk-directed therapy is intended to improve not only the cure rates in ALL, but also the quality of life of the patients, in terms of decreased acute morbidity and long-term sequelae. 2 As we continue to learn more about the mechanisms of leukemic cell transformation and the development of drug resistance, as well as the germline genetic influences on a patient’s responses to chemotherapy, the closer we are to an era of personalized therapy for ALL, in which common protocols for large groups of patients will be replaced by treatments based on the unique molecular targets and pharmacodynamics of individual patients. 3 In this issue of Seminars in Hematology, a group of distinguished investigators review the current and emerging concepts of leukemia pathobiology and therapy, emphasizing issues that must be addressed if we expect to eradicate ALL without undue side effects that may preclude a normal productive life.Leukemia is caused by sequential alterations in proto-oncogenes, tumor-suppressor genes, and microRNA genes of hematopoietic stem cells or their committed progenitors. 3, 4 These fundamental changes alter key regulatory processes in target cells by unleashing an unlimited capacity for self-renewal, subverting the controls of normal proliferation, blocking cell differentiation, and promoting resistance to death signals (apoptosis). 3, 4 Despite remarkable progress in cataloging the molecular lesions that are common to ALL, our understanding of how such changes cooperate to produce overt ALL is still rudimentary at best. Mullighan and Downing address this problem by adroitly discussing recent advances in the use of highresolution genome-wide platforms to detect DNA copy number abnormalities and regions of loss-of-heterozygosity. Together with transcriptional profiling, these studies can be used to determine interactions among tumor-suppressor genes and other oncogenic lesions that not only provide valuable mechanistic insights, but may also qualify as useful targets for therapy. 5, 6 The authors have taken considerable care to highlight some of the technical aspects of data
在儿童急性淋巴细胞白血病中，处于免疫表型成熟不同阶段的母细胞具有干细胞特性。
影响因子：
50.3
作者：
le Viseur C;Hotfilder M;Bomken S;Wilson K;Röttgers S;Schrauder A;Rosemann A;Irving J;Stam RW;Shultz LD;Harbott J;Jürgens H;Schrappe M;Pieters R;Vormoor J
通讯作者：
Vormoor J
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.