Pasquer Hélène, Tostain Maëlys, Kaci Nina, Roux Blandine, Benajiba Lina
Université de Paris, APHP, Hôpital Saint-Louis, 75010 Paris, France.
INSERM UMR 944, Institut de Recherche Saint-Louis, 75010 Paris, France.
Cancers (Basel). 2021 Feb 11;13(4):748. doi: 10.3390/cancers13040748.
Over the past decades, genetic advances have allowed a more precise molecular characterization of AML with the identification of novel oncogenes and tumor suppressors as part of a comprehensive AML molecular landscape. Recent advances in genetic sequencing tools also enabled a better understanding of AML leukemogenesis from the preleukemic state to posttherapy relapse. These advances resulted in direct clinical implications with the definition of molecular prognosis classifications, the development of treatment recommendations based on minimal residual disease (MRD) measurement and the discovery of novel targeted therapies, ultimately improving AML patients' overall survival. The more recent development of functional genomic studies, pushed by novel molecular biology technologies (short hairpin RNA (shRNA) and CRISPR-Cas9) and bioinformatics tools design on one hand, along with the engineering of humanized physiologically relevant animal models on the other hand, have opened a new genomics era resulting in a greater knowledge of AML physiopathology. Combining descriptive and functional genomics will undoubtedly open the road for an AML cure within the next decades.
在过去几十年中，遗传学进展使得对急性髓系白血病（AML）能够进行更精确的分子特征描述，鉴定出了新的致癌基因和肿瘤抑制基因，这构成了AML全面分子格局的一部分。基因测序工具的最新进展也使人们能更好地理解AML从白血病前期状态到治疗后复发的白血病发生过程。这些进展产生了直接的临床影响，包括定义分子预后分类、基于微小残留病（MRD）检测制定治疗建议以及发现新的靶向疗法，最终改善了AML患者的总生存期。一方面，受新型分子生物学技术（短发夹RNA（shRNA）和CRISPR-Cas9）及生物信息学工具设计的推动，另一方面受人性化生理相关动物模型构建的推动，功能基因组学研究的最新发展开启了一个新的基因组学时代，使人们对AML生理病理学有了更多了解。结合描述性基因组学和功能基因组学无疑将在未来几十年为治愈AML铺平道路。
