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They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98\u2010BPTF (NB) fusion in patients with T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) using next\u2010generation sequencing. The FG\u2010repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline\u2010inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T\u2010ALL cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto\u2010oncogene\n                      <jats:italic>Pim1<\/jats:italic>\n                      , which encodes a serine\/threonine kinase. NB transcriptionally regulated\n                      <jats:italic>Pim1<\/jats:italic>\n                      expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB\u2010induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T\u2010ALL cells by inactivating the pro\u2010apoptotic protein BCL2\u2010associated agonist of cell death (BAD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion\u2010positive leukemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.7445","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T07:50:59Z","timestamp":1719561059000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["NUP98\u2010BPTF promotes oncogenic transformation through PIM1 upregulation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1311-6908","authenticated-orcid":false,"given":"Mina","family":"Noura","sequence":"first","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of 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