Rodríguez David, Bretones Gabriel, Arango Javier R, Valdespino Víctor, Campo Elías, Quesada Víctor, López-Otín Carlos
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología-IUOPA, Universidad de Oviedo, 33006, Oviedo, Spain.
Int J Hematol. 2015 Mar;101(3):219-28. doi: 10.1007/s12185-015-1733-0. Epub 2015 Jan 29.
In spite of being the most prevalent adult leukemia in Western countries, the molecular mechanisms driving the establishment and progression of chronic lymphocytic leukemia (CLL) remain largely unknown. In recent years, the use of next-generation sequencing techniques has uncovered new and, in some cases, unexpected driver genes with prognostic and therapeutic value. The mutational landscape of CLL is characterized by high-genetic and epigenetic heterogeneity, low mutation recurrence and a long tail of cases with undefined driver genes. On the other hand, the use of deep sequencing has also revealed high intra-tumor heterogeneity and provided a detailed picture of clonal evolution processes. This phenomenon, in which aberrant DNA methylation can also participate, appears to be tightly associated to poor outcomes and chemo-refractoriness, thus providing a new subject for therapeutic intervention. Hence, and having in mind the limitations derived from the CLL complexity thus described, the application of massively parallel sequencing studies has unveiled a wealth of information that is expected to substantially improve patient staging schemes and CLL clinical management.
尽管慢性淋巴细胞白血病（CLL）是西方国家最常见的成人白血病，但其驱动疾病发生和进展的分子机制仍不清楚。近年来，新一代测序技术的应用发现了具有预后和治疗价值的新驱动基因，在某些情况下，这些基因是意想不到的。CLL的突变图谱具有高度的遗传和表观遗传异质性、低突变复发率以及存在大量未明确驱动基因的病例。另一方面，深度测序的应用也揭示了肿瘤内的高度异质性，并提供了克隆进化过程的详细情况。这种异常DNA甲基化也可能参与的现象似乎与不良预后和化疗难治性密切相关，从而为治疗干预提供了新靶点。因此，考虑到上述CLL复杂性所带来的局限性，大规模平行测序研究的应用揭示了大量信息，有望显著改善患者的分期方案和CLL的临床管理。
