| Autor: |
Philomina Sona Peramangalam, Sridevi Surapally, Shikan Zheng, Robert Burns, Nan Zhu, Sridhar Rao, Carsten Muller-Tidow, John A. Pulikkan |
| Rok vydání: |
2023 |
| Popis: |
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 novelMYCNenhancer, 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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