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bioRxiv · 10.1101/2023.03.03.531018

N-MYC regulates Cell Survival via eIF4G1 in inv(16) Acute Myeloid Leukemia

Peramangalam, P. S.·Surapally, S.·Zheng, S.·Burns, R.·Zhu, N.·Rao, S.·Muller-Tidow, C.·Pulikkan, J. A.
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Abstract

c-MYC and N-MYC are critical regulators of hematopoietic stem cell activity. While the role of c-MYC deregulation is studied in detail in hematological malignancies, 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 crucial to the survival and maintenance of inv(16) leukemia. We identified a novel 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. Ours is the first report to demonstrate the oncogenic role of eIF4G1 in AML. Our results reveal a mechanism whereby N-MYC drives a leukemic transcriptional program and provide a rationale for the therapeutic targeting of the N-MYC/eIF4G1 axis in myeloid leukemia.

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Peramangalam, P. S., Surapally, S., Zheng, S., Burns, R., Zhu, N., Rao, S., Muller-Tidow, C., Pulikkan, J. A.. 2023-03-06. N-MYC regulates Cell Survival via eIF4G1 in inv(16) Acute Myeloid Leukemia. https://doi.org/10.1101/2023.03.03.531018

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