Yu Xue Xin, Chen Ai Li, Li Yue Ying, Liu Dan, Wang Qian Fei
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Bejijng 100101, China.
Yi Chuan. 2018 Nov 20;40(11):988-997. doi: 10.16288/j.yczz.18-188.
Leukemia is a group of hematologic malignancy that has unfavorable prognosis and unclear mechanisms. In recent years, advances in leukemia research encompass the discovery of novel targets in acute myeloid leukemia drug resistance, epigenetic crosstalk in mixed lineage leukemia (MLL) leukemogenesis, genetic mechanisms of aggressive NK-cell leukemia, as well as the critical role of key epigenetic regulator in acute myeloid malignancy. Remarkably, researchers revealed that the histone modifying gene SETD2 as a new tumor suppressor and therapeutic target in patients with acute myeloid leukemia. Furthermore, low-dose chemotherapy as a frontline regiment in treating pediatric acute myeloid leukemia can substantially reduce the toxic side effects and treatment costs without impairing efficacy. Although advances in cancer genomics have greatly increased our understanding of the molecular characteristics in tumor biology, recent studies suggest that Darwinian evolution of intratumor heterogeneity represents a major challenge to develop therapeutic strategies to improve disease control. Researchers also dissected the distinct evolutionary dynamics under different chemotherapy regimens and the corresponding applications in the evaluation of treatment outcomes. Altogether, these efforts offered new opportunities for the development of acute myeloid leukemia diagnostics and therapeutics.
白血病是一组预后不良且发病机制不明的血液系统恶性肿瘤。近年来,白血病研究取得的进展包括在急性髓系白血病耐药性方面发现新靶点、混合谱系白血病(MLL)白血病发生过程中的表观遗传相互作用、侵袭性NK细胞白血病的遗传机制,以及关键表观遗传调节因子在急性髓系恶性肿瘤中的关键作用。值得注意的是,研究人员发现组蛋白修饰基因SETD2是急性髓系白血病患者的一种新的肿瘤抑制因子和治疗靶点。此外,低剂量化疗作为治疗儿童急性髓系白血病的一线方案,在不影响疗效的情况下可大幅降低毒副作用和治疗成本。尽管癌症基因组学的进展极大地增进了我们对肿瘤生物学分子特征的理解,但最近的研究表明,肿瘤内异质性的达尔文进化是制定改善疾病控制治疗策略的一项重大挑战。研究人员还剖析了不同化疗方案下独特的进化动力学及其在评估治疗结果中的相应应用。总之,这些努力为急性髓系白血病的诊断和治疗带来了新机遇。