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Full-Text Articles in Pathology
Loss Of Cbl And Cbl-B Ubiquitin Ligases Abrogates Hematopoietic Stem Cell Quiescence And Sensitizes Leukemic Disease To Chemotherapy., Wei An, Scott A. Nadeau, Bhopal C. Mohapatra, Dan Feng, Neha Zutshi, Matthew D. Storck, Priyanka Arya, James E. Talmadge, Jane L. Meza, Vimla Band, Hamid Band
Loss Of Cbl And Cbl-B Ubiquitin Ligases Abrogates Hematopoietic Stem Cell Quiescence And Sensitizes Leukemic Disease To Chemotherapy., Wei An, Scott A. Nadeau, Bhopal C. Mohapatra, Dan Feng, Neha Zutshi, Matthew D. Storck, Priyanka Arya, James E. Talmadge, Jane L. Meza, Vimla Band, Hamid Band
Journal Articles: Pathology and Microbiology
Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is unclear. Here we demonstrate that HSC expansion and MPD development upon combined Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated that DKO HSCs exhibit reduced quiescence associated with compromised reconstitution …