Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B
Year: 2012
Type: article
Abstract: Ribosomal protein (RP) mutations in diseases such as 5q- syndrome both disrupt hematopoiesis and increase the risk of developing hematologic malignancy. However, the mechanism by which RP mutations increase cancer risk has remained an important unanswered question. We show here that monoallelic, germline inactivation of the ribosomal protein L22 (Rpl22) predisposes T-lineage progenitors to transformation. Indeed, RPL22 was found to be inactivated in ∼ 10% of human T-acute lymphoblastic leukemias. Moreover, monoallelic loss of Rpl22 accelerates development of thymic lymphoma in both a mouse model of T-cell malignancy and in acute transformation assays in vitro. We show that Rpl22 inactivation enhances transformation potential through induction of the stemness factor, Lin28B. Our finding that Rpl22 inactivation promotes transformation by inducing expression of Lin28B provides the first insight into the mechanistic basis by which mutations in Rpl22, and perhaps some other RP genes, increases cancer risk.
Source: Blood
Authors: Shuyun Rao, Sang-Yun Lee, Alejandro Gutierrez, Jacqueline Perrigoue, Roshan J. Thapa, Zhigang Tu, John R. Jeffers, Michele Rhodes, Stephen Anderson, Tamas Oravecz, Stephen P. Hunger, Roman A. Timakhov, Rugang Zhang, Siddharth Balachandran, Gerard P. Zambetti, Joseph R. Testa, A. Thomas Look, David L. Wiest
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G118882467, G1542604717, G156276794, G2135062745, G221190914, G261408449, G2901481919, G301932103, G3147759870, G3402416433, Support for Human Specimen Banking in NCI-Sponsored Clinical Trials-(CGB), G421865639, G46340935, G47070370, Therapeutic Index of Acute Lymphoblastic Leukemia, G499207949, G662899963, G806545856, G8243034, Center for Molecular Studies in Digestive and Liver Diseases, G997771125
OpenAlex ID: W2020574069