Pui Ching-Hon
Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105-2794, USA.
J Formos Med Assoc. 2004 Feb;103(2):85-95.
Contemporary risk-directed therapy has advanced the cure rate for childhood acute lymphoblastic leukemia to near 80%. Molecular genetic analyses of leukemic cells, pharmacodynamic studies of antileukemic agents, and pharmacogenetic studies of the host's drug-metabolizing enzymes, drug transporters, and drug targets are providing a rational base for further improvement of treatment efficacy and the reduction of complications. Early treatment response, as defined by the measurement of minimal residual disease, which reflects both the drug responsiveness of leukemic cells and host pharmacodynamics/pharmacogenomics, is the most reliable prognostic indicator for gauging the intensity of treatment. Recent advances in high-throughput biotechnology, including gene expression profiling, proteomics and gene silencing promise to identify molecular targets for specific treatment. The ultimate goal is to elucidate central mechanisms of leukemogenesis so that preventive measures can be devised.
当代风险导向治疗已将儿童急性淋巴细胞白血病的治愈率提高到近80%。白血病细胞的分子遗传学分析、抗白血病药物的药效学研究以及宿主药物代谢酶、药物转运体和药物靶点的药物遗传学研究，为进一步提高治疗效果和减少并发症提供了合理依据。通过测量微小残留病来定义的早期治疗反应反映了白血病细胞的药物反应性以及宿主的药效学/药物基因组学，是衡量治疗强度最可靠的预后指标。包括基因表达谱分析、蛋白质组学和基因沉默在内的高通量生物技术的最新进展有望确定特定治疗的分子靶点。最终目标是阐明白血病发生的核心机制，以便制定预防措施。
