Pui Ching-Hon
Departments of Oncology and Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA,
Front Med. 2015 Mar;9(1):1-9. doi: 10.1007/s11684-015-0381-3. Epub 2014 Dec 15.
With the cure rate of childhood acute lymphoblastic leukemia (ALL) approaching 90%, further improvement in the treatment outcome and quality of life of patients will require better understanding of the mechanisms of drug resistance, identifying new leukemic cell genetic lesions that are amendable to available target therapy, and optimizing treatment based on host pharmacodynamics and pharmacogenomics. Deeper characterization of leukemic cell genetic abnormalities has discovered new subtypes of leukemia such as early T-cell precursor ALL and Philadelphia chromosome-like ALL, and identified many genomic alterations that have diagnostic, prognostic, or therapeutic implications. In this regard, several novel fusion transcripts are responsive to ABL tyrosine kinase inhibitors and potentially to JAK inhibitors. Genome-wide analyses have also unraveled the role of inherited cancer predisposing genes and small nucleotide polymorphisms of several genes in the development of childhood ALL. These advances promise to lead to more sophisticated personalized treatment strategies in the near future.
随着儿童急性淋巴细胞白血病（ALL）的治愈率接近90%，若要进一步改善患者的治疗效果和生活质量，就需要更好地了解耐药机制，识别可采用现有靶向治疗的新的白血病细胞基因损伤，并根据宿主药效学和药物基因组学优化治疗方案。对白血病细胞基因异常的深入表征发现了白血病的新亚型，如早期T细胞前体ALL和费城染色体样ALL，并确定了许多具有诊断、预后或治疗意义的基因组改变。在这方面，几种新型融合转录本对ABL酪氨酸激酶抑制剂有反应，可能对JAK抑制剂也有反应。全基因组分析还揭示了遗传性癌症易感基因以及几个基因的单核苷酸多态性在儿童ALL发生中的作用。这些进展有望在不久的将来带来更精密的个性化治疗策略。
