Tasian Sarah K, Hunger Stephen P
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and Abramson Cancer Center, Philadelphia, PA, USA.
Br J Haematol. 2017 Mar;176(6):867-882. doi: 10.1111/bjh.14474. Epub 2016 Dec 16.
Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (i) underlying biological and clinical characteristics, and (ii) depth of initial treatment response with appropriate modulation of chemotherapy intensity. This review describes the current mutational landscape of childhood ALL and discusses opportunities for substantial improvements in survival with implementation of molecularly targeted therapies.
急性淋巴细胞白血病（ALL）的基因和表观遗传学分析取得了重大进展，加深了对初发和复发ALL关键生物学亚群的认识，从而改善了患者的风险分层。这些成果进一步明确了与白血病相关的关键通路和体细胞改变，这些通路和改变可能对激酶抑制剂、表观遗传疗法或其他新型药物的治疗尤为敏感。目前儿童ALL的治疗成功依赖于根据以下因素对患者进行精确的风险分层：（i）潜在的生物学和临床特征，以及（ii）初始治疗反应的深度，并适当调整化疗强度。本综述描述了儿童ALL当前的突变格局，并讨论了通过实施分子靶向疗法大幅提高生存率的机会。
