Ancos-Pintado Raquel, Bragado-García Irene, Morales María Luz, García-Vicente Roberto, Arroyo-Barea Andrés, Rodríguez-García Alba, Martínez-López Joaquín, Linares María, Hernández-Sánchez María
Department of Translational Hematology, Instituto de Investigación Hospital 12 de Octubre (imas12), Hematological Malignancies Clinical Research Unit H12O-CNIO, CIBERONC, ES 28041 Madrid, Spain.
Department of Biochemistry and Molecular Biology, Pharmacy School, Universidad Complutense de Madrid, ES 28040 Madrid, Spain.
Cancers (Basel). 2022 Jul 25;14(15):3612. doi: 10.3390/cancers14153612.
CRISPR is becoming an indispensable tool in biological research, revolutionizing diverse fields of medical research and biotechnology. In the last few years, several CRISPR-based genome-targeting tools have been translated for the study of hematological neoplasms. However, there is a lack of reviews focused on the wide uses of this technology in hematology. Therefore, in this review, we summarize the main CRISPR-based approaches of high throughput screenings applied to this field. Here we explain several libraries and algorithms for analysis of CRISPR screens used in hematology, accompanied by the most relevant databases. Moreover, we focus on (1) the identification of novel modulator genes of drug resistance and efficacy, which could anticipate relapses in patients and (2) new therapeutic targets and synthetic lethal interactions. We also discuss the approaches to uncover novel biomarkers of malignant transformations and immune evasion mechanisms. We explain the current literature in the most common lymphoid and myeloid neoplasms using this tool. Then, we conclude with future directions, highlighting the importance of further gene candidate validation and the integration and harmonization of the data from CRISPR screening approaches.
CRISPR正成为生物学研究中不可或缺的工具，给医学研究和生物技术的各个领域带来变革。在过去几年里，几种基于CRISPR的基因组靶向工具已被用于血液肿瘤的研究。然而，缺乏专注于该技术在血液学中广泛应用的综述。因此，在本综述中，我们总结了应用于该领域的基于CRISPR的高通量筛选的主要方法。在此，我们解释了几种用于分析血液学中CRISPR筛选的文库和算法，并介绍了最相关的数据库。此外，我们重点关注：（1）鉴定耐药性和疗效的新型调节基因，这可以预测患者的复发情况；（2）新的治疗靶点和合成致死相互作用。我们还讨论了发现恶性转化新生物标志物和免疫逃逸机制的方法。我们用该工具解释了最常见的淋巴和髓系肿瘤的当前文献。然后，我们总结了未来的方向，强调了进一步验证基因候选物以及整合和协调CRISPR筛选方法数据的重要性。
