CRISPR/Cas13d Screen Identifies the Long Non-Coding RNA GAS5 as a Vulnerability in AML

Louisa Hagen

Document Type

Article

Publication Date

2025

Keywords

JGM

Abstract

Acute myeloid leukemia (AML) is a heterogenous blood cancer characterized by the accumulation of myeloblasts, immature white blood cells. Unlike many solid tumors, AML typically harbors fewer genetic mutations on average and exhibits a high rate of relapse with few additional mutations being found. This suggests that non-genetic mechanisms play a critical role in AML pathogenesis. One such non-genetic mechanism is the participation of long non-coding RNAs (lncRNAs) which recently have been recognized to play a role in cancer development. To systematically uncover lncRNAs essential for AML survival and proliferation, we have conducted an extensive CRISPR/Cas13d RNA-targeting screen of over 7,000 annotated human lncRNAs. Among the top-scoring lncRNAs identified in our screen was GAS5, for which our preliminary data demonstrated a critical role in supporting AML cell proliferation.

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