Laboratory for High Throughput Biology, Institute for Research in Immunology and Cancer, Montréal, QC, Canada.
Centre de recherche en infectiologie du CHUL, Centre de recherche du CHU de Québec, Quebec City, QC, Canada; CHU de Québec Hôpital Enfant-Jésus, Quebec City, QC, Canada; Department of Medicine, Université Laval, Quebec City, QC, Canada.
Exp Hematol. 2019 Jun;74:1-12. doi: 10.1016/j.exphem.2019.05.003. Epub 2019 May 30.
Leukemia is a complex genetic disease caused by errors in differentiation, growth, and apoptosis of hematopoietic cells in either lymphoid or myeloid lineages. Large-scale genomic characterization of thousands of leukemia patients has produced a tremendous amount of data that have enabled a better understanding of the differences between adult and pediatric patients. For instance, although phenotypically similar, pediatric and adult myeloid leukemia patients differ in their mutational profiles, typically involving either chromosomal translocations or recurrent single-base-pair mutations, respectively. To elucidate the molecular mechanisms underlying the biology of this cancer, continual efforts have been made to develop more contextually and biologically relevant experimental models. Leukemic cell lines, for example, provide an inexpensive and tractable model but often fail to recapitulate critical aspects of tumor biology. Likewise, murine leukemia models of leukemia have been highly informative but also do not entirely reproduce the human disease. More recent advances in the development of patient-derived xenografts (PDXs) or human models of leukemias are poised to provide a more comprehensive, and biologically relevant, approach to directly assess the impact of the in vivo environment on human samples. In this review, the advantages and limitations of the various current models used to functionally define the genetic requirements of leukemogenesis are discussed.
白血病是一种复杂的遗传性疾病，由淋巴或髓系造血细胞在分化、生长和凋亡过程中的错误引起。对数千名白血病患者进行的大规模基因组特征分析产生了大量数据，使人们能够更好地理解成人和儿童患者之间的差异。例如，尽管表型相似，但儿科和成人髓系白血病患者的突变谱不同，分别涉及染色体易位或反复出现的单个碱基对突变。为了阐明这种癌症生物学的分子机制，人们一直在努力开发更具上下文和生物学相关性的实验模型。例如，白血病细胞系提供了一种廉价且易于处理的模型，但往往无法再现肿瘤生物学的关键方面。同样，白血病的小鼠白血病模型虽然提供了丰富的信息，但也不完全复制人类疾病。最近在开发患者来源的异种移植物（PDX）或人类白血病模型方面的进展有望提供一种更全面、更具生物学相关性的方法，直接评估体内环境对人类样本的影响。在这篇综述中，讨论了用于功能定义白血病发生的遗传要求的各种当前模型的优缺点。
