Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-024-01489-6 Dr. Srikanth Kodali et al.
Points
- The study identified that acute myeloid leukemia (AML) cells have abnormally high P-bodies compared to normal hematopoietic progenitors.
- Disruption of P-body assembly hindered the initiation and maintenance of AML while having minimal effect on normal steady-state hematopoiesis and regenerative hematopoiesis.
- P-bodies in AML cells trap mRNAs that encode tumor suppressors, preventing their translation and contributing to leukemia progression.
- Dissolving P-bodies releases trapped mRNAs, leading to significant gene expression and chromatin structure changes, specifically in leukemia cells.
- The study suggests that targeting P-bodies could offer new therapeutic strategies for treating AML. This could potentially disrupt leukemia progression while sparing normal hematopoietic functions.
Summary
In a comprehensive study addressing post-transcriptional control mechanisms, researchers used genome-wide CRISPR screens to uncover the pivotal role of P-bodies in acute myeloid leukemia (AML). Their investigation revealed that AML cells possess abnormally high P-bodies compared to normal hematopoietic progenitors. The disruption of P-body assembly was detrimental to initiating and maintaining AML, yet it displayed minimal impact on steady-state hematopoiesis and influenced regenerative hematopoiesis.
Molecular analysis of P-bodies isolated from human AML cells highlighted their essential function in trapping mRNAs that encode significant tumor suppressors, excluding them from translation. The liberated mRNAs were translated upon dissolution of P-bodies, leading to a substantial alteration in gene expression and chromatin structure, specifically in leukemia cells. This mechanism suggests a distinct and critical role for RNA sequestration in P-bodies within cancer progression versus normal tissue homeostasis.
The findings from this study elucidate the unique contribution of P-bodies to the pathophysiology of myeloid leukemia, contrasting their role in normal cellular processes. By understanding the specific functions of P-bodies in AML, new pathways for potential therapeutic interventions emerge, offering hope for targeted treatments that disrupt leukemia progression while preserving normal hematopoietic functions.
Link to the article: https://www.nature.com/articles/s41556-024-01489-6
References Kodali, S., Proietti, L., Valcarcel, G., López-Rubio, A. V., Pessina, P., Eder, T., Shi, J., Jen, A., Lupión-Garcia, N., Starner, A. C., Bartels, M. D., Cui, Y., Sands, C. M., Planas-Riverola, A., Martínez, A., Velasco-Hernandez, T., Tomás-Daza, L., Alber, B., Manhart, G., … Di Stefano, B. (2024). RNA sequestration in P-bodies sustains myeloid leukaemia. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-024-01489-6
