Study of Rpl22 in MDS and AML.

摘要

Increasing evidence from our lab and others support the findings that ribosomal proteins play critical role in development as well as bone marrow disease in addition to its essential role in protein synthesis. We found Rpl22 is dispensable for protein biosynthesis but regulating transformation and hematopoiesis. Previously I had determined that Rpl22 functions as a haploinsufficient tumor suppressor in mouse T-cell lymphoma model by activating the NFkappaB and its target Lin28B. Recently we also found that Rpl22 knockout mice exhibit MDS-like phenotype associated with anemia and abnormal bone marrow (BM) hematopoiesis. Consistent with what we observed in mouse model, our collaborator found that Rpl22 was mutated or deleted in some MDS and AML patients. With all these data, I intend to investigate the role of Rpl22 in MDS and its predisposition of AML. I found that Rpl22 loss induces Lin28B is specific and the activation of NFkappaB and Lin28B induction depends on ER stress PERK signaling. By introducing AML oncogenic gene MLL-AF9 into the BM transplant mouse model, we found Rpl22 inactivation accelerates AML progression. We are still in the progress of investigating Rpl22 in MDS/AML and hopefully can find new therapeutic target through these efforts.