Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Hematology Am Soc Hematol Educ Program. 2011;2011:36-42. doi: 10.1182/asheducation-2011.1.36.
In recent years, research in molecular genetics has been instrumental in deciphering the molecular pathogenesis of acute myeloid leukemia (AML). With the advent of the novel genomics technologies such as next-generation sequencing, it is expected that virtually all genetic lesions in AML will soon be identified. Gene mutations or deregulated expression of genes or sets of genes now allow us to explore the enormous diversity among cytogenetically defined subsets of AML, in particular the large subset of cytogenetically normal AML. Nonetheless, there are several challenges, such as discriminating driver from passenger mutations, evaluating the prognostic and predictive value of a specific mutation in the concert of the various concurrent mutations, or translating findings from molecular disease pathogenesis into novel therapies. Progress is unlikely to be fast in developing molecular targeted therapies. Contrary to the initial assumption, the development of molecular targeted therapies is slow and the various reports of promising new compounds will need to be put into perspective because many of these drugs did not show the expected effects.
近年来，分子遗传学的研究在解析急性髓系白血病（AML）的分子发病机制方面发挥了重要作用。随着新一代测序等新型基因组学技术的出现，预计 AML 中的几乎所有遗传病变很快就会被识别出来。基因突变或基因或基因集的表达失调，使我们能够探索 AML 中在细胞遗传学上定义明确的亚组之间的巨大多样性，特别是在细胞遗传学上正常的 AML 的大部分。尽管如此，仍存在一些挑战，例如区分驱动突变和乘客突变，评估特定突变在各种并发突变中的预后和预测价值，或将分子疾病发病机制的研究结果转化为新的治疗方法。开发分子靶向疗法的进展不太可能很快。与最初的假设相反，分子靶向疗法的发展缓慢，并且需要对各种有前途的新化合物的报告进行客观评估，因为许多这些药物并没有显示出预期的效果。
