Faculty Collaboration Database

N-MYC regulates cell survival via eIF4G1 in inv(16) acute myeloid leukemia. Sci Adv 2024 Mar;10(9):eadh8493

Date

02/28/2024

Pubmed ID

38416825

Pubmed Central ID

PMC10901375

DOI

10.1126/sciadv.adh8493

Scopus ID

2-s2.0-85186742316 (requires institutional sign-in at Scopus site)

Abstract

N-MYC (encoded by MYCN) is a critical regulator of hematopoietic stem cell function. While the role of N-MYC deregulation is well established in neuroblastoma, the importance of N-MYC deregulation in leukemogenesis remains elusive. Here, we demonstrate that N-MYC is overexpressed in acute myeloid leukemia (AML) cells with chromosome inversion inv(16) and contributes to the survival and maintenance of inv(16) leukemia. We identified a previously unknown MYCN enhancer, active in multiple AML subtypes, essential for MYCN mRNA levels and survival in inv(16) AML cells. We also identified eukaryotic translation initiation factor 4 gamma 1 (eIF4G1) as a key N-MYC target that sustains leukemic survival in inv(16) AML cells. The oncogenic role of eIF4G1 in AML has not been reported before. Our results reveal a mechanism whereby N-MYC drives a leukemic transcriptional program and provides a rationale for the therapeutic targeting of the N-MYC/eIF4G1 axis in myeloid leukemia.

Author List

Peramangalam PS, Surapally S, Veltri AJ, Zheng S, Burns R, Zhu N, Rao S, Muller-Tidow C, Bushweller JH, Pulikkan JA

Authors

John A. Pulikkan PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Carcinogenesis
Cell Survival
Hematopoietic Stem Cells
Humans
Leukemia, Myeloid, Acute
N-Myc Proto-Oncogene Protein