The MA Reader IGF2BP2 Regulates Glutamine Metabolism and Represents a Therapeutic Target in Acute Myeloid Leukemia

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2022 Oct 28

PMID 36306790

Authors

Hengyou Weng

Feng Huang

Zhaojin Yu

Zhenhua Chen

Emily Prince

Yalin Kang

Keren Zhou

Wei Li

Jiacheng Hu

Chen Fu

Tursunjan Aziz

Hongzhi Li

Jingwen Li

Ying Yang

Li Han

Subo Zhang

Yuelong Ma

Mingli Sun

Huizhe Wu

Zheng Zhang

Mark Wunderlich

Sean Robinson

Daniel Braas

Johanna Ten Hoeve

Bin Zhang

Guido Marcucci

James C Mulloy

Keda Zhou

Hong-Fang Tao

Xiaolan Deng

David Horne

Minjie Wei

Huilin Huang

Jianjun Chen

Affiliations

Soon will be listed here.

Abstract

N-Methyladenosine (mA) modification and its modulators play critical roles and show promise as therapeutic targets in human cancers, including acute myeloid leukemia (AML). IGF2BP2 was recently reported as an mA binding protein that enhances mRNA stability and translation. However, its function in AML remains largely elusive. Here we report the oncogenic role and the therapeutic targeting of IGF2BP2 in AML. High expression of IGF2BP2 is observed in AML and associates with unfavorable prognosis. IGF2BP2 promotes AML development and self-renewal of leukemia stem/initiation cells by regulating expression of critical targets (e.g., MYC, GPT2, and SLC1A5) in the glutamine metabolism pathways in an mA-dependent manner. Inhibiting IGF2BP2 with our recently identified small-molecule compound (CWI1-2) shows promising anti-leukemia effects in vitro and in vivo. Collectively, our results reveal a role of IGF2BP2 and mA modification in amino acid metabolism and highlight the potential of targeting IGF2BP2 as a promising therapeutic strategy in AML.

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