Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Leukemia. 2018 Jul;32(7):1493-1499. doi: 10.1038/s41375-018-0029-9. Epub 2018 Jan 30.
There are few instances in oncology where reciprocal clinical and laboratory translation studies have accelerated the understanding of disease biology and treatment more so than the decade following the Food and Drug Administration (FDA) approval of lenalidomide (Revlimid; Celgene Corporation, Summit, NJ, USA) for the treatment of patients with myelodysplastic syndrome (MDS) and chromosome 5q deletion (del(5q)). Lenalidomide was approved by the FDA in December 2005 on the merits of a multicenter phase 2 study, which demonstrated sustained and prolonged transfusion independence in the majority of participants. Since then, del(5q) MDS has emerged as one of the best characterized bone marrow malignancies and, in particular, has raised our understanding as to how allelic haplodeficiency underlies both its hematological phenotype and the selective sensitivity to lenalidomide by virtue of synthetic lethality. Herein, we review the clinical and biological discoveries that have advanced our understanding of del(5q) MDS and its treatment since its approval by United States and European regulatory agencies.
在肿瘤学领域，很少有实例能像 FDA 批准来那度胺（Revlimid；Celgene Corporation，Summit，NJ，USA）用于治疗骨髓增生异常综合征（MDS）和 5 号染色体缺失（del(5q)）患者后十年那样，更能促进对疾病生物学和治疗的理解。来那度胺于 2005 年 12 月获得 FDA 的批准，其依据是一项多中心 2 期研究的结果，该研究表明大多数参与者的输血独立性得到了持续和延长。自那时以来，del(5q) MDS 已成为最具特征的骨髓恶性肿瘤之一，特别是提高了我们对等位基因单倍体缺失如何构成其血液学表型以及通过合成致死性对来那度胺的选择性敏感性的理解。在此，我们回顾了自美国和欧洲监管机构批准以来，在临床和生物学方面推进我们对 del(5q) MDS 及其治疗理解的发现。
