Novel insights in chronic lymphocytic leukemia: Are we getting closer to understanding the pathogenesis of the disease?
Novel insights in chronic lymphocytic leukemia: Are we getting closer to understanding the pathogenesis of the disease?
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DOI：
10.1200/jco.2007.15.4393
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发表时间：
2008-09-20
影响因子：
45.3
通讯作者：
Ghia, Paolo
中科院分区：
文献类型：
--
作者：
Caligaris-Cappio, Federico;Ghia, Paolo
慢性淋巴细胞白血病（CLL）具有独特的流行病学、生物学和临床特征。逐渐出现的图片使我们认为，恶性CLL细胞的关键基因是那些由精细的细胞遗传学和分子研究揭示的许多microRNA调控的基因，关键分子是B细胞受体（BCR）。CLL细胞可能通过某种抗原压力选择的假设被许多发现所加强，这些发现表明BCR介导的刺激在疾病的自然史中起相关作用，并且自身抗原以及有助于消除和清除凋亡细胞和病原菌的分子结构可能与触发和/或促进CLL的演变有关。一个重要的问题是，微小的单克隆B细胞群体表型上类似于CLL（发生在约3.5%的健康个体的外周血中，被称为单克隆B淋巴细胞增多症）是否可能是CLL发展的关键步骤。CLL的所有相关事件都发生在组织中，其中许多细胞和分子相互作用形成有利于恶性细胞积聚的微环境，并有利于增殖细胞在形成假滤泡增殖中心的可变大小的局灶性聚集体中的组织化。鉴于了解慢性淋巴细胞白血病的发病机制可能对新的治疗方法的发展产生的影响，本综述的目的是讨论慢性淋巴细胞白血病的新见解是否使我们更接近理解疾病的宗旨;定义新出现的，刺激的问题;并展开仍然需要解决的主要挑战。
Chronic lymphocytic leukemia (CLL) has unique epidemiologic, biologic, and clinical features. The progressively emerging picture leads us to consider that the critical genes for malignant CLL cells are those regulated by a number of microRNAs revealed by refined cytogenetic and molecular studies, and that the key molecule is the B-cell receptor (BCR). The hypothesis that CLL cells might be selected by some sort of antigenic pressure is strengthened by numerous findings indicating that a BCR-mediated stimulation plays a relevant role in the natural history of the disease and that autoantigens, as well as molecular structures instrumental in eliminating and scavenging apoptotic cells and pathogenic bacteria, may be relevant in triggering and/or facilitating the evolution of CLL. An important question is whether the tiny monoclonal B-cell populations phenotypically similar to CLL (that occur in the peripheral blood of about 3.5% of healthy individuals and are termed monoclonal B lymphocytosis) might be a critical step in the development of CLL. All relevant events of CLL occur in tissues in which a number of cellular and molecular interactions shape a microenvironment conducive to the accumulation of malignant cells and favor the organization of proliferating cells in focal aggregates of variable size that form the pseudofollicular proliferation centers. Given the impact that understanding the pathogenesis of CLL might have on the development of new treatments, the purposes of this review are to discuss whether the novel insights in CLL are leading us closer to understanding the tenet of the disease; to define the emerging new, stimulating questions; and to unfold the major challenges that still need to be addressed.