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Study of RpI22 in MDS and AML

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Technical Report,30 Sep 2013,29 Sep 2016

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The Institute for Cancer Research Philadelphia United States

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Increasing evidence from our lab and others suggests that ribosomal proteins play a critical regulatory role in development and disease, including bone marrow disease, that can be mediated independently of their functions in ribosomal biosynthesis. Previously I have determined that ribosomal protein Rpl22 functions as a haploinsufficient tumor suppressor by activating NFB and its target Lin28B in a mouse T-cell lymphoma model driven by Myr-Akt2. Recently we also found that Rpl22 knockout mice exhibit an MDS-like phenotype associated with anemia and abnormal bone marrow BM hematopoiesis. Consistently, our collaborator found that RPL22 indeed was mutated or deleted in some MDS and AML patients. Further we found that loss of Rpl22 but not other ribosomal proteins induces Lin28B, and the activation of NFB and Lin28B mainly depends on ER stress signaling through PERK. Rpl22 has a homolog Rpl22-Like1 Like1 that is induced upon Rpl22 loss. Interestingly, Rpl22 functions through the regulation of Like1. Like1 overexpression is both necessary and sufficient for both transformation and NFB-mediated Lin28B induction. Mechanistic studies revealed that Rpl22 directly bind to Like1 mRNA and inhibit its translation. Through MLL-AF9 AML BM transplant mouse model, I found that Rpl22 inactivation accelerates AML progression and correlated with poor survival. We are still in the progress of investigate Rpl22 and its paralog Like1 in MDSAML and hopefully can find out new therapeutic target through these efforts.


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  • Medicine and Medical Research

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