Therapeutic Target Discovery Using High-Throughput Genetic Screens in Acute Myeloid Leukemia

Abstract

The development of high-throughput gene manipulating tools such as short hairpin RNA (shRNA) and CRISPR/Cas9 libraries has enabled robust characterization of novel functional genes contributing to the pathological states of the diseases. In acute myeloid leukemia (AML), these genetic screen approaches have been used to identify effector genes with previously unknown roles in AML. These AML-related genes centralize alongside the cellular pathways mediating epigenetics, signaling transduction, transcriptional regulation, and energy metabolism. The shRNA/CRISPR genetic screens also realized an array of candidate genes amenable to pharmaceutical targeting. This review aims to summarize genes, mechanisms, and potential therapeutic strategies found via high-throughput genetic screens in AML. We also discuss the potential of these findings to instruct novel AML therapies for combating drug resistance in this genetically heterogeneous disease.

Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine

“…However, gene therapy is currently still at an early stage. The development of high-throughput gene manipulating using CRISPR-cas9 can be of interest in re-expressing ENT1 or dCK in the future [ 37 ]. In addition, other approaches may be used to induce ENT1 expression.…”

The Art of Finding the Right Drug Target: Emerging Methods and Strategies

“…Joint analysis of multiple methods and multiple data provides the possibility for a more comprehensive understanding of disease mechanisms (Li et al, 2022c;Wang et al, 2022a;Rodrigues and Bernardes 2020). For example, the continuous advancement and development of related technologies such as high-throughput sequencing, omics technology, and CRISPR-based library screening have greatly changed the form of drug target discovery (Liu et al, 2020;Kumar et al, 2024). In addition, the emergence of emerging drug target discovery strategies such as DARTS and NMD has injected new impetus into drug target discovery.…”

Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis

“…Gene knockdown and knockout screens are powerful genetic approaches to identifying novel effector genes in biological systems. [ 34 ] Since 2010, multiple RNAi or CRISPR library screens have been performed in EwS and revealed critical mechanisms mediating the EwS maintenance and therapeutic response (summarized in Table S3 , Supporting Information). [ 35 ] Despite these advances, an epigenetic‐focused CRISPR screen (Figure 1A,B ) has never been reported in EwS.…”