The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia

N6-Methyladenosine (m6A) 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 m6A 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 m6A-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 m6A modification in amino acid metabolism and highlight the potential of targeting IGF2BP2 as a promising therapeutic strategy in AML.

 

Comments:

That's an intriguing study! It seems like the research sheds light on the significance of N6-methyladenosine (m6A) modification and its association with IGF2BP2 in acute myeloid leukemia (AML). The identification of IGF2BP2 as an m6A binding protein influencing mRNA stability and translation is particularly noteworthy.

The findings linking high IGF2BP2 expression in AML to unfavorable prognosis and its role in promoting AML development and self-renewal of leukemia stem/initiation cells through the regulation of key targets in glutamine metabolism pathways provide valuable insights into the disease's mechanisms.

Moreover, the development of a small-molecule compound (CWI1-2) that inhibits IGF2BP2 and demonstrates promising anti-leukemia effects both in vitro and in vivo represents a potential therapeutic avenue for AML. Targeting IGF2BP2 could be a crucial strategy in combating AML by disrupting amino acid metabolism pathways.

This research not only highlights the significance of m6A modification and IGF2BP2 in AML but also suggests a novel therapeutic approach that could potentially improve treatment outcomes for patients.

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Cat.No.	Product Name	Information
E1327	CWI1-2 hydrochloride	CWI1-2 hydrochloride is an inhibitor of IGF2BP2 that binds IGF2BP2 and inhibits its interaction with m6A-modified target transcripts, induces apoptosis and differentiation, and shows promising anti-leukemic effects.

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