{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:57:30Z","timestamp":1790269050735,"version":"4.1.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Acute myeloid leukemia (AML) is a heterogeneous disease characterized by malignant proliferation of myeloid hematopoietic stem\/progenitor cells. NPM1 represents the most frequently mutated gene in AML and approximately 30% of AML cases carry NPM1 mutations. Mutated NPM1 result in the cytoplasmic localization of NPM1 (NPM1c). NPM1c interacts with other proteins to block myeloid differentiation, promote cell proliferation and impair DNA damage repair. NPM1 is a good prognostic marker, but some patients ultimately relapse or fail to respond to therapy. It is urgent for us to find optimal therapies for NPM1-mutated AML. Efficacy of multiple drugs is under investigation in NPM1-mutated AML, and several clinical trials have been registered. In this review, we summarize the present knowledge of therapy and focus on the possible therapeutic interventions for NPM1-mutated AML.<\/jats:p>","DOI":"10.3389\/fonc.2022.972606","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T10:08:43Z","timestamp":1664273323000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Targeted therapy in NPM1-mutated AML: Knowns and unknowns"],"prefix":"10.3389","volume":"12","author":[{"given":"Rong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Lin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Zhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Hu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041974","article-title":"Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype","volume":"352","author":"Falini","year":"2005","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90241-9","article-title":"Major nucleolar proteins shuttle between nucleus and cytoplasm","volume":"56","author":"Borer","year":"1989","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1282","article-title":"Temporal and spatial control of nucleophosmin by the ran-Crm1 complex in centrosome duplication","volume":"7","author":"Wang","year":"2005","journal-title":"Nat Cell Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.26.10.3798-3809.2006","article-title":"Nucleophosmin is essential for ribosomal protein L5 nuclear export","volume":"26","author":"Yu","year":"2006","journal-title":"Mol Cell Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.66.2239","article-title":"Tryptophans 286 and 288 in the c-terminal region of protein B23.1 are important for its nucleolar localization","volume":"66","author":"Nishimura","year":"2002","journal-title":"Biosci Biotechnol Biochem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003278200","article-title":"Mapping the functional domains of nucleolar protein B23","volume":"275","author":"Hingorani","year":"2000","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)00093-3","article-title":"Nucleophosmin\/B23 is a target of Cdk2\/Cyclin e in centrosome duplication","volume":"103","author":"Okuda","year":"2000","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.24.3.985-996.2004","article-title":"Physical and functional interactions of the arf tumor suppressor protein with Nucleophosmin\/B23","volume":"24","author":"Bertwistle","year":"2004","journal-title":"Mol Cell Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ncb814","article-title":"Nucleophosmin regulates the stability and transcriptional activity of P53","volume":"4","author":"Colombo","year":"2002","journal-title":"Nat Cell Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4745","article-title":"Both carboxy-terminus nes motif and mutated Tryptophan(S) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in npmc+ aml","volume":"107","author":"Falini","year":"2006","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-07-0273","article-title":"Born to be exported: Cooh-terminal nuclear export signals of different strength ensure cytoplasmic accumulation of nucleophosmin leukemic mutants","volume":"67","author":"Bolli","year":"2007","journal-title":"Cancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7150\/thno.19439","article-title":"Npm1 mutant mediated pml delocalization and stabilization enhances autophagy and cell survival in leukemic cells","volume":"7","author":"Zou","year":"2017","journal-title":"Theranostics"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci97117","article-title":"Leukemogenic nucleophosmin mutation disrupts the transcription factor hub that regulates granulomonocytic fates","volume":"128","author":"Gu","year":"2018","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1083\/jcb.200711040","article-title":"Nucleophosmin and its aml-associated mutant regulate c-myc turnover through Fbw7 gamma","volume":"182","author":"Bonetti","year":"2008","journal-title":"J Cell Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.251","article-title":"Functional regulation of the Apurinic\/Apyrimidinic endonuclease 1 by nucleophosmin: Impact on tumor biology","volume":"33","author":"Vascotto","year":"2014","journal-title":"Oncogene"},{"key":"B16","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1200\/jco.2009.25.1496","article-title":"Favorable prognostic impact of Npm1 mutations in older patients with cytogenetically normal De novo acute myeloid leukemia and associated gene- and microrna-expression signatures: A cancer and leukemia group b study","volume":"28","author":"Becker","year":"2010","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.104133","article-title":"Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in Npm1-mutated patients identifies those at high risk of relapse","volume":"99","author":"Hubmann","year":"2014","journal-title":"Haematologica"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-109090","article-title":"The impact of Flt3 internal tandem duplication mutant level, number, size, and interaction with Npm1 mutations in a Large cohort of young adult patients with acute myeloid leukemia","volume":"111","author":"Gale","year":"2008","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/335440a0","article-title":"Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-b cells","volume":"335","author":"Vaux","year":"1988","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.11.3091.3091","article-title":"High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy","volume":"81","author":"Campos","year":"1993","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-13-0609","article-title":"Selective bcl-2 inhibition by abt-199 causes on-target cell death in acute myeloid leukemia","volume":"4","author":"Pan","year":"2014","journal-title":"Cancer Discovery"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-16-0313","article-title":"Efficacy and biological correlates of response in a phase ii study of venetoclax monotherapy in patients with acute myelogenous leukemia","volume":"6","author":"Konopleva","year":"2016","journal-title":"Cancer Discovery"},{"key":"B23","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1182\/blood-2018-08-868752","article-title":"Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia","volume":"133","author":"DiNardo","year":"2019","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and venetoclax in previously untreated acute myeloid leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1200\/jco.18.01600","article-title":"Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: Results from a phase Ib\/Ii study","volume":"37","author":"Wei","year":"2019","journal-title":"J Clin Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020004856","article-title":"Venetoclax plus ldac for newly diagnosed aml ineligible for intensive chemotherapy: A phase 3 randomized placebo-controlled trial","volume":"135","author":"Wei","year":"2020","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.00572","article-title":"Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (Caveat): A phase ib dose-escalation study of venetoclax combined with modified intensive chemotherapy","volume":"38","author":"Chua","year":"2020","journal-title":"J Clin Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.03736","article-title":"Venetoclax combined with flag-Ida induction and consolidation in newly diagnosed and relapsed or refractory acute myeloid leukemia","volume":"39","author":"DiNardo","year":"2021","journal-title":"J Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000243","article-title":"Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia","volume":"3","author":"Winters","year":"2019","journal-title":"Blood Adv"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S316561","article-title":"Efficacy of venetoclax combined with decitabine-based treatment for heavily pre-treated relapsed or refractory aml patients in a real-world setting","volume":"13","author":"Tong","year":"2021","journal-title":"Cancer Manag Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.649209","article-title":"Outcomes of adults with Relapsed\/Refractory acute myeloid leukemia treated with venetoclax plus hypomethylating agents at a comprehensive cancer center","volume":"11","author":"Tenold","year":"2021","journal-title":"Front Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1182\/blood-2019-122477%JBlood","article-title":"Venetoclax combined with cladribine + low dose arac (Ldac) alternating with 5-azacytidine produces high rates of minimal residual disease (Mrd) negative complete remissions (Cr) in older patients with newly diagnosed acute myeloid leukemia (Aml)","volume":"134","author":"Kadia","year":"2019","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"5081","DOI":"10.1182\/blood-2019-121816%JBlood","article-title":"Venetoclax-based regimen for treatment of patients with acute myeloid leukemia in community based practices","volume":"134","author":"Law","year":"2019","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1182\/blood-2020-139794%JBlood","article-title":"Factors associated with clinical outcomes after venetoclax-based combination therapy in acute myeloid leukemia and high-grade myeloid neoplasms","volume":"136","author":"Madanat","year":"2020","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-142780%JBlood","article-title":"Outcomes of therapy with venetoclax combined with hypomethylating agents in favorable-risk acute myeloid leukemia (Aml)","volume":"136","author":"Arslan","year":"2020","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-141380%JBlood","article-title":"Response patterns and mrd by flow cytometry and ngs in patients with mutant-idh acute myeloid leukemia treated with venetoclax in combination with hypomethylating agents","volume":"136","author":"Hammond","year":"2020","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1182\/blood-2021-154059%JBlood","article-title":"Npm1 mutations do not retain a favorable prognostic impact in adults with advanced relapsed or refractory (R\/R) acute myeloid leukemia (Aml)","volume":"138","author":"Venugopal","year":"2021","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1182\/blood-2021-153227%JBlood","article-title":"Phase ii trial of ten-day decitabine with venetoclax (Dec10-ven) in acute myeloid leukemia: Updated outcomes in genomic subgroups","volume":"138","author":"Maiti","year":"2021","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4413","DOI":"10.1182\/blood-2021-148259%JBlood","article-title":"Safety and short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: A single institution experience","volume":"138","author":"Yu","year":"2021","journal-title":"Blood"},{"key":"B40","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41375-019-0485-x","article-title":"Genetic characterization of abt-199 sensitivity in human aml","volume":"34","author":"Bisaillon","year":"2020","journal-title":"Leukemia"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001267","article-title":"Outcomes of older patients with Npm1-mutated aml: Current treatments and the promise of venetoclax-based regimens","volume":"4","author":"Lachowiez","year":"2020","journal-title":"Blood Adv"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16722","article-title":"Venetoclax induces rapid elimination of Npm1 mutant measurable residual disease in combination with low-intensity chemotherapy in acute myeloid leukaemia","volume":"192","author":"Tiong","year":"2021","journal-title":"Br J Haematol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208868","article-title":"Arsenic trioxide induces regulated, death receptor-independent cell death through a bcl-2-Controlled pathway","volume":"24","author":"Scholz","year":"2005","journal-title":"Oncogene"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1101\/gad.182980.111","article-title":"Anti-apoptotic mcl-1 is essential for the development and sustained growth of acute myeloid leukemia","volume":"26","author":"Glaser","year":"2012","journal-title":"Genes Dev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/srep27696","article-title":"Targeting mcl-1\/Bcl-Xl forestalls the acquisition of resistance to abt-199 in acute myeloid leukemia","volume":"6","author":"Lin","year":"2016","journal-title":"Sci Rep"},{"key":"B46","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s40164-021-00221-6","article-title":"Arsenic trioxide synergistically promotes the antileukaemic activity of venetoclax by downregulating mcl-1 in acute myeloid leukaemia cells","volume":"10","author":"Cho","year":"2021","journal-title":"Exp Hematol Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25719","article-title":"Venetoclax and arsenic showed synergistic anti-leukemia activity in vitro and in vivo for acute myeloid leukemia with the Npm1 mutation","volume":"95","author":"Zhu","year":"2020","journal-title":"Am J Hematol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.ccell.2018.08.005","article-title":"Mutant Npm1 maintains the leukemic state through hox expression","volume":"34","author":"Brunetti","year":"2018","journal-title":"Cancer Cell"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-16-0237","article-title":"Targeting chromatin regulators inhibits leukemogenic gene expression in Npm1 mutant leukemia","volume":"6","author":"K\u00fchn","year":"2016","journal-title":"Cancer Discovery"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax5863","article-title":"Therapeutic targeting of preleukemia cells in a mouse model of Npm1 mutant acute myeloid leukemia","volume":"367","author":"Uckelmann","year":"2020","journal-title":"Science"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011917","article-title":"Menin inhibition decreases bcl-2 and synergizes with venetoclax in Npm1\/Flt3-mutated aml","volume":"138","author":"Carter","year":"2021","journal-title":"Blood"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005037","article-title":"Synergistic targeting of Flt3 mutations in aml Via combined menin-mll and Flt3 inhibition","volume":"136","author":"Dzama","year":"2020","journal-title":"Blood"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006575","article-title":"Combinatorial treatment with menin and Flt3 inhibitors induces complete remission in aml models with activating Flt3 mutations","volume":"136","author":"Miao","year":"2020","journal-title":"Blood"},{"key":"B54","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1182\/blood-2020-134942%JBlood","article-title":"Preliminary data on a phase 1\/2a first in human study of the menin-Kmt2a (Mll) inhibitor ko-539 in patients with relapsed or refractory acute myeloid leukemia","volume":"136","author":"Wang","year":"2020","journal-title":"Blood"},{"key":"B55","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1182\/blood-2021-146944%JBlood","article-title":"Safety and efficacy of menin inhibition in patients (Pts) with mll-rearranged and Npm1 mutant acute leukemia: A phase (Ph) 1, first-in-Human study of sndx-5613 (Augment 101)","volume":"138","author":"Stein","year":"2021","journal-title":"Blood"},{"key":"B56","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.tcb.2007.02.003","article-title":"Crm1-mediated nuclear export: To the pore and beyond","volume":"17","author":"Hutten","year":"2007","journal-title":"Trends Cell Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13886","article-title":"Inhibition of Xpo1 enhances cell death induced by abt-199 in acute myeloid leukaemia Via mcl-1","volume":"22","author":"Luedtke","year":"2018","journal-title":"J Cell Mol Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-607648","article-title":"Decitabine priming enhances the antileukemic effects of exportin 1 (Xpo1) selective inhibitor selinexor in acute myeloid leukemia","volume":"125","author":"Ranganathan","year":"2015","journal-title":"Blood"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0550-8","article-title":"A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia","volume":"11","author":"Wang","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16804","article-title":"A phase ii study of selinexor plus cytarabine and idarubicin in patients with Relapsed\/Refractory acute myeloid leukaemia","volume":"190","author":"Fiedler","year":"2020","journal-title":"Br J Haematol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.145","article-title":"Kpt-8602, a second-generation inhibitor of Xpo1-mediated nuclear export, is well tolerated and highly active against aml blasts and leukemia-initiating cells","volume":"31","author":"Etchin","year":"2017","journal-title":"Leukemia"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.136","article-title":"Next-generation Xpo1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies","volume":"30","author":"Hing","year":"2016","journal-title":"Leukemia"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000359","article-title":"Venetoclax response is enhanced by selective inhibitor of nuclear export compounds in hematologic malignancies","volume":"4","author":"Fischer","year":"2020","journal-title":"Blood Adv"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3978","article-title":"Arsenic-induced pml targeting onto nuclear bodies: Implications for the treatment of acute promyelocytic leukemia","volume":"94","author":"Zhu","year":"1997","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.222","article-title":"Role of cysteine 288 in nucleophosmin cytoplasmic mutations: Sensitization to toxicity induced by arsenic trioxide and bortezomib","volume":"27","author":"Huang","year":"2013","journal-title":"Leukemia"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-611459","article-title":"Arsenic trioxide and all-trans retinoic acid target Npm1 mutant oncoprotein levels and induce apoptosis in Npm1-mutated aml cells","volume":"125","author":"Martelli","year":"2015","journal-title":"Blood"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-612416","article-title":"Retinoic acid and arsenic trioxide trigger degradation of mutated Npm1, resulting in apoptosis of aml cells","volume":"125","author":"El Hajj","year":"2015","journal-title":"Blood"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.274878","article-title":"A Pin1\/Pml\/P53 axis activated by retinoic acid in npm-1c-Acute myeloid leukemia","volume":"106","author":"Hleihel","year":"2021","journal-title":"Haematologica"},{"key":"B69","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3324\/haematol.13378","article-title":"Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. results from the amlsg trial aml Hd98b","volume":"94","author":"Schlenk","year":"2009","journal-title":"Haematologica"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.48.12.2094","article-title":"Basis of actinomycin action. i. DNA binding and inhibition of rna-polymerase synthetic reactions by actinomycin","volume":"48","author":"Goldberg","year":"1962","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01192-7","article-title":"Dactinomycin induces complete remission associated with nucleolar stress response in Relapsed\/Refractory Npm1-mutated aml","volume":"35","author":"Gionfriddo","year":"2021","journal-title":"Leukemia"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1509584","article-title":"Dactinomycin in Npm1-mutated acute myeloid leukemia","volume":"373","author":"Falini","year":"2015","journal-title":"N Engl J Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13438","article-title":"Dactinomycin in acute myeloid leukemia with Npm1 mutations","volume":"105","author":"Beziat","year":"2020","journal-title":"Eur J Haematol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-21-0177","article-title":"Actinomycin d targets Npm1c-primed mitochondria to restore pml-driven senescence in aml therapy","volume":"11","author":"Wu","year":"2021","journal-title":"Cancer Discovery"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2014.04.001","article-title":"The past and future of Cd33 as therapeutic target in acute myeloid leukemia","volume":"28","author":"Laszlo","year":"2014","journal-title":"Blood Rev"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-398370","article-title":"Correlation of Cd33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood aml","volume":"119","author":"Pollard","year":"2012","journal-title":"Blood"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-523548","article-title":"Cd33 target validation and sustained depletion of aml blasts in long-term cultures by the bispecific T-Cell-Engaging antibody amg 330","volume":"123","author":"Krupka","year":"2014","journal-title":"Blood"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.043786","article-title":"High Cd33 expression levels in acute myeloid leukemia cells carrying the nucleophosmin (Npm1) mutation","volume":"96","author":"De Propris","year":"2011","journal-title":"Haematologica"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(12)60485-1","article-title":"Effect of gemtuzumab ozogamicin on survival of adult patients with de-Novo acute myeloid leukaemia (Alfa-0701): A randomised, open-label, phase 3 study","volume":"379","author":"Castaigne","year":"2012","journal-title":"Lancet"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.01406","article-title":"Gemtuzumab ozogamicin in Npm1-mutated acute myeloid leukemia: Early results from the prospective randomized amlsg 09-09 phase iii study","volume":"38","author":"Schlenk","year":"2020","journal-title":"J Clin Oncol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nm730","article-title":"Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion","volume":"8","author":"Dong","year":"2002","journal-title":"Nat Med"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-394395%JBlood","article-title":"Mutated regions of nucleophosmin 1 elicit both Cd4+ and Cd8+ T-cell responses in patients with acute myeloid leukemia","volume":"120","author":"Greiner","year":"2012","journal-title":"Blood"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-496844","article-title":"Immune responses against the mutated region of cytoplasmatic Npm1 might contribute to the favorable clinical outcome of aml patients with Npm1 mutations (Npm1mut)","volume":"122","author":"Greiner","year":"2013","journal-title":"Blood"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.176461","article-title":"Acute myeloid leukemia with mutated nucleophosmin 1: An immunogenic acute myeloid leukemia subtype and potential candidate for immune checkpoint inhibition","volume":"102","author":"Greiner","year":"2017","journal-title":"Haematologica"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112823","article-title":"High pd-L1 expression predicts for worse outcome of leukemia patients with concomitant Npm1 and Flt3 mutations","volume":"20","author":"Brodsk\u00e1","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1038\/s41467-020-15364-z","article-title":"Npm1 upregulates the transcription of pd-L1 and suppresses T cell activity in triple-negative breast cancer","volume":"11","author":"Qin","year":"2020","journal-title":"Nat Commun"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33690","article-title":"A phase 1b\/2 study of azacitidine with pd-L1 antibody avelumab in Relapsed\/Refractory acute myeloid leukemia","volume":"127","author":"Saxena","year":"2021","journal-title":"Cancer"},{"key":"B88","doi-asserted-by":"publisher","first-page":"E46","DOI":"10.1002\/ajh.26043","article-title":"A phase I clinical trial of avelumab in combination with decitabine as first line treatment of unfit patients with acute myeloid leukemia","volume":"96","author":"Zheng","year":"2021","journal-title":"Am J Hematol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0070-8","article-title":"Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes","volume":"32","author":"Daver","year":"2018","journal-title":"Leukemia"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.09.006","article-title":"Epigenetic strategies synergize with pd-L1\/Pd-1 targeted cancer immunotherapies to enhance antitumor responses","volume":"10","author":"Chen","year":"2020","journal-title":"Acta Pharm Sin B"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/nature18945","article-title":"Neoantigen landscape dynamics during human melanoma-T cell interactions","volume":"536","author":"Verdegaal","year":"2016","journal-title":"Nature"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.02.005","article-title":"Targeting cancer-specific mutations by T cell receptor gene therapy","volume":"33","author":"Blankenstein","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-299990","article-title":"Acute myeloid leukemia with mutated nucleophosmin (Npm1): Is it a distinct entity","volume":"117","author":"Falini","year":"2011","journal-title":"Blood"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1172\/jci97482","article-title":"Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia","volume":"129","author":"van der Lee","year":"2019","journal-title":"J Clin Invest"},{"key":"B95","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41551-020-00625-5","article-title":"Car-T cells targeting a nucleophosmin neoepitope exhibit potent specific activity in mouse models of acute myeloid leukaemia","volume":"5","author":"Xie","year":"2021","journal-title":"Nat BioMed Eng"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689","article-title":"Genomic and epigenomic landscapes of adult De novo acute myeloid leukemia","volume":"368","author":"Ley","year":"2013","journal-title":"N Engl J Med"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic classification and prognosis in acute myeloid leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N Engl J Med"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1038\/s41467-021-21233-0","article-title":"Biological and therapeutic implications of a unique subtype of Npm1 mutated aml","volume":"12","author":"Mer","year":"2021","journal-title":"Nat Commun"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008211","article-title":"How I diagnose and treat Npm1-mutated aml","volume":"137","author":"Falini","year":"2021","journal-title":"Blood"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507471","article-title":"Assessment of minimal residual disease in standard-risk aml","volume":"374","author":"Ivey","year":"2016","journal-title":"New Engl J Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.972606\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T10:08:47Z","timestamp":1664273327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.972606\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":100,"alternative-id":["10.3389\/fonc.2022.972606"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.972606","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]},"article-number":"972606"}}