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As an important epigenetic regulator,\n                    <jats:italic>PHF6<\/jats:italic>\n                    mutations frequently coexist with\n                    <jats:italic>JAK3<\/jats:italic>\n                    mutations in T-ALL patients. However, the role(s) of\n                    <jats:italic>PHF6<\/jats:italic>\n                    mutations in JAK3-driven leukemia remain unclear. Here, the cooperation between JAK3 activation and PHF6 inactivation is examined in leukemia patients and in mice models. We found that the average survival time is shorter in patients with\n                    <jats:italic>JAK\/STAT<\/jats:italic>\n                    and\n                    <jats:italic>PHF6<\/jats:italic>\n                    comutation than that in other patients, suggesting a potential role of PHF6 in leukemia progression. We subsequently found that\n                    <jats:italic>Phf6<\/jats:italic>\n                    deficiency promotes\n                    <jats:italic>JAK3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M511I<\/jats:italic>\n                    <\/jats:sup>\n                    -induced T-ALL progression in mice by inhibiting the Bai1-Mdm2-P53 signaling pathway, which is independent of the JAK3\/STAT5 signaling pathway. Furthermore, combination therapy with a JAK3 inhibitor (tofacitinib) and a MDM2 inhibitor (idasanutlin) reduces the\n                    <jats:italic>Phf6<\/jats:italic>\n                    KO and\n                    <jats:italic>JAK3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M511I<\/jats:italic>\n                    <\/jats:sup>\n                    leukemia burden in vivo. Taken together, our study suggests that combined treatment with JAK3 and MDM2 inhibitors may potentially increase the drug benefit for T-ALL patients with\n                    <jats:italic>PHF6<\/jats:italic>\n                    and\n                    <jats:italic>JAK3<\/jats:italic>\n                    comutation.\n                  <\/jats:p>","DOI":"10.1038\/s41375-021-01392-1","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T02:02:38Z","timestamp":1630375358000},"page":"370-382","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["PHF6 and JAK3 mutations cooperate to drive T-cell acute lymphoblastic leukemia progression"],"prefix":"10.1038","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-3672","authenticated-orcid":false,"given":"Shengnan","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-5061","authenticated-orcid":false,"given":"Xiaomin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaibing","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengxiao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6239-1519","authenticated-orcid":false,"given":"Yajing","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8531-0483","authenticated-orcid":false,"given":"Jun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4395-1095","authenticated-orcid":false,"given":"Tao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-5022","authenticated-orcid":false,"given":"Weiping","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"1392_CR1","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/nrc.2016.63","volume":"16","author":"L Belver","year":"2016","unstructured":"Belver L, Ferrando A. 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