Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities
Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities
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DOI：
10.1182/blood-2010-07-155663
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发表时间：
2011-02-10
期刊：
影响因子：
20.3
通讯作者：
Ferrarini, Manlio
中科院分区：
文献类型：
--
作者：
Chiorazzi, Nicholas;Ferrarini, Manlio
几种类型的细胞被认为引起慢性淋巴细胞白血病（CLL），这些建议反映了当时可用技术的复杂性。尽管对于该疾病的正常细胞对应物尚未达成共识，但基于表面膜表型和基因表达谱，抗原经历的B淋巴细胞似乎是必需的。然而，目前尚不清楚的是，是否单个或多个正常前体被刺激进化成CLL，以及在哪个阶段发生。一个统一的、简洁的理论是，具有突变或未突变ighv的CLL克隆来自边缘区B细胞。然而，在一些CLL克隆中发现的非常相似的b细胞受体氨基酸序列和多抗原和自身抗原结合活性的显著差异，对CLL的单细胞衍生提出了挑战。在这一观点中，我们总结了关于CLL细胞正常对应体的数据，并建议在确定这种疾病的细胞起源时，考虑白血病发生的多步骤过程是很重要的。最后，虽然现有的数据不能明确地确定细胞的起源，但我们提供了单细胞和多细胞起源模型作为稻草人的可能性，这些模型可以改进，并有希望找到这个难题的最终答案。[血液杂志];2011;117(6):1781-1791。]
Several cell types have been suggested as giving rise to chronic lymphocytic leukemia (CLL), and these suggestions have reflected the sophistication of technology available at the time. Although there is no consensus as to the normal cellular counterpart(s) in the disease, an antigen-experienced B lymphocyte appears required based on surface membrane phenotypes and gene expression profiles. However, what is still unclear is whether a single or multiple normal pre-cursors were stimulated to evolve into CLL and at what stage( s) this occurred. A unifying, parsimonious theory is that CLL clones with either mutated or unmutated IGHVs derive from marginal zone B cells. However, evidence for remarkably similar B-cell receptor amino acid sequence and striking differences in polyantigen and autoantigen-binding activity, found in some but not all CLL clones, challenge a single-cell derivation for CLL. In this Perspective, we summarize data regarding normal counterparts of CLL cells and suggest that a multistep process of leukemogenesis is important to consider when assigning a cellular origin for this disease. Finally, although available data do not definitively identify the cell( s) of origin, we offer possibilities for single- and multiple-cell origin models as straw men that can be improved on and hopefully lead to final answers to this puzzle. (Blood. 2011; 117( 6): 1781-1791)