Department of Pediatrics, Helen Diller Family Cancer Research Building, University of California, San Francisco, San Francisco, California 94158-9001.
Comprehensive Cancer Center, Helen Diller Family Cancer Research Building, University of California, San Francisco, San Francisco, California 94158-9001.
Cold Spring Harb Perspect Med. 2018 Apr 2;8(4):a031526. doi: 10.1101/cshperspect.a031526.
genes are mutated in 5%-40% of a spectrum of myeloid and lymphoid cancers with affected 2-3 times more often than Genomic analysis indicates that mutations generally occur as secondary events in leukemogenesis, but are integral to the disease phenotype. The tractable nature of the hematopoietic system has facilitated generating accurate mouse models of hematologic malignancies characterized by hyperactive Ras signaling. These strains provide robust platforms for addressing how oncogenic s expression perturbs proliferation, differentiation, and self-renewal programs in stem and progenitor cell populations, for testing potential therapies, and for investigating mechanisms of drug response and resistance. This review summarizes recent insights from key studies in mouse models of hematologic cancer that are broadly relevant for understanding Ras biology and for ongoing efforts to implement rational therapeutic strategies for cancers with oncogenic mutations.
在髓系和淋巴系癌症的范围内，有 5%-40%的基因发生了突变，受影响的频率比 基因高出 2-3 倍。基因组分析表明，突变通常是白血病发生过程中的继发事件，但却是疾病表型的重要组成部分。造血系统的可处理性使得生成特征为 Ras 信号过度活跃的血液恶性肿瘤的精确小鼠模型成为可能。这些品系为解决致癌 s 表达如何扰乱干细胞和祖细胞群体的增殖、分化和自我更新程序提供了强大的平台，用于测试潜在的治疗方法，并研究药物反应和耐药性的机制。这篇综述总结了血液恶性肿瘤的小鼠模型中一些关键研究的最新见解，这些见解对于理解 Ras 生物学以及正在进行的针对具有致癌 突变的癌症实施合理治疗策略的努力具有广泛的意义。
