High-Throughput CRISPR Screening in Hematological Neoplasms

SIMPLE SUMMARY: High-throughput CRISPR screening provides an unbiased way for functional genomic studies in hematological malignancies. This approach has been used to study different blood cancers aiming to identify modulator genes for drug efficacy, therapeutic targets, synthetic lethal interactions, biomarkers of malignant transformation and the genetic determinants of immune evasion. In this review, we discuss the most relevant CRISPR screening studies in the field of hematology. ABSTRACT: 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.