title: Autophagy collaborates with ubiquitination to downregulate oncoprotein E2A/Pbx1 in B-cell acute lymphoblastic leukemia.
abstract: B-cell acute lymphoblastic leukemia (B-ALL) accounts for the most cancer incidences in children. We present here that autophagy is downregulated in pediatric B-ALL, suggesting a possible link between autophagy failure and pediatric B-ALL leukemogenesis. With a pediatric t(1;19) B-ALL xenograft mouse model, we show here that activation of autophagy by preventive administration of rapamycin improved the survival of leukemia animals by partial restoration of hematopoietic stem/progenitor cells, whereas treatment of the animals with rapamycin caused leukemia bone marrow cell-cycle arrest. Activation of autophagy in vitro or in vivo by rapamycin or starvation downregulated oncogenic fusion protein E2A/Pbx1. Furthermore, E2A/Pbx1 was found to be colocalized with autophagy marker LC3 in autolysosomes and with ubiquitin in response to autophagy stimuli, whereas autophagy or ubiquitination inhibitor blocked these colocalizations. Together, our data suggest a collaborative action between autophagy and ubiquitination in the degradation of E2A/Pbx1, thereby revealing a novel strategy for targeted preventive or treatment therapy on the pediatric ALL.
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: N
authors.initials: N
authors.lastname: Yuan
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Lin
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: A
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D054875:Ubiquitination / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; C089847:E2A-Pbx1 fusion protein