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Numerous studies using mTOR inhibitors have shown that mTOR targeting suppresses gene expression and cell proliferation. However, mTOR-targeted cancer therapies have seen very limited success, and evasive resistance to mTOR-targeted drugs needs to be addressed. By examining\n                    <jats:italic>mTOR<\/jats:italic>\n                    gene-deleted mouse hematopoietic stem cells, which show a loss of quiescence and hyperproliferation, we uncovered the activation of the ERK\/MNK\/eIF4E\/RNA polymerase II\/c-Myc axis as an adaptive mechanism to\n                    <jats:italic>mTOR<\/jats:italic>\n                    loss that results in increased chromatin accessibility and activated global gene expression, allowing the cells to hyperproliferate. The work also implicates a potential strategy for overcoming evasive resistance in mTOR-targeted therapies for leukemia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2020102118","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T11:54:30Z","timestamp":1608724470000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["Adaptive responses to\n                    <i>mTOR<\/i>\n                    gene targeting in hematopoietic stem cells reveal a proliferative mechanism evasive to mTOR inhibition"],"prefix":"10.1073","volume":"118","author":[{"given":"Cuiqing","family":"Fan","sequence":"first","affiliation":[{"name":"Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229;"},{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, 201102 Shanghai, 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