Applying CRISPR-Cas9 screens to dissect hematological malignancies

Abstract

Bit by bit functional genomic tools have been piecing together the molecular puzzle driving tumorigenesis in human patients since the last few decades. Nevertheless, our understanding of the role of several genes and regulatory elements that drive critical cancer-associated physiological processes from disease development to progression to spread is abysmal, which significantly impacts our ability of applying these insights in the context of improved disease management. The recent advent of CRISPR-Cas9-based technology and its application in cancer genomics has however allowed the generation of a wealth of knowledge that has helped decipher several critical questions associated with translational cancer research. Precisely, the high throughput capability coupled with an extreme level of technological plasticity associated with the CRISPR-Cas9 screens have expanded our horizons from merely struggling to appreciate cancer as a genetic disease to observing at the integrated genomic/epigenomic network of numerous malignancies and correlating it with our present knowledge of drugging strategies to develop innovative approaches for next generation cancer precision medicine. Specifically, within blood cancers, current CRISPR screens have specifically focused on improving our understanding of drug resistance strategies, disease biology, development of novel therapeutic approaches, and identifying the molecular mechanisms of current therapies, with an underlying aim of improving disease outcomes. Here, we review the development of CRISPR-Cas9 genome editing strategy, explicitly focusing on the recent advances in the CRISPR-Cas9 based screening approaches, its current capabilities, limitations, and future applications in the context of hematological malignancies.