{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:28:32Z","timestamp":1787138912382,"version":"build-2736575974"},"reference-count":110,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where \u201cone-size-fits-all\u201d chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on shaping the therapeutic approach, including the integration of targeted therapies such as FLT3 and menin inhibitors into frontline therapy. Furthermore, pediatric AML treatment options are being driven by recent discoveries in adult AML, broadening their clinical trials to include pediatric patients, in part due to the RACE for Children Act that went into effect in August 2020. This review identifies the most prevalent high-risk cytogenetic lesions in pediatric AML, emphasizing their incidence, prognostic significance, and implications for clinical management. By synthesizing current research on these key genetic abnormalities and their associated therapies, we aim to provide an updated perspective on the evolving landscape of high-risk pediatric AML management that can then lead to the establishment of an agile framework to rapidly evaluate, approve, and deploy novel agents.<\/jats:p>","DOI":"10.3390\/cancers18162686","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:04:12Z","timestamp":1787137452000},"page":"2686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A New Paradigm for Pediatric AML: Improving the Pipeline for Treatments Targeting Cytogenetic and Molecular Alterations"],"prefix":"10.3390","volume":"18","author":[{"given":"Camila","family":"Ayerbe","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern, Dallas, TX 77030, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Nunez","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Leukemia\/Lymphoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX 77070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4869-8818","authenticated-orcid":false,"given":"Irtiza N.","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Children\u2019s Cancer Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Garcia-Manero","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Cuglievan","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Leukemia\/Lymphoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX 77070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9146-4702","authenticated-orcid":false,"given":"Amber","family":"Gibson","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Leukemia\/Lymphoma Section, The University of Texas MD Anderson Cancer Center, Houston, TX 77070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.31557\/APJCP.2020.21.5.1487","article-title":"GLOBAL Leukemia in Children 0\u201314 Statistics 2018, Incidence and Mortality and Human Development Index (HDI): GLOBOCAN Sources and Methods","volume":"21","author":"Namayandeh","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/pbc.24464","article-title":"Epidemiology of childhood acute myeloid leukemia","volume":"60","author":"Puumala","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e30584","DOI":"10.1002\/pbc.30584","article-title":"Children\u2019s Oncology Group\u2019s 2023 blueprint for research: Myeloid neoplasms","volume":"70","author":"Cooper","year":"2023","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Quessada, J., Cuccuini, W., Saultier, P., Loosveld, M., Harrison, C.J., and Lafage-Pochitaloff, M. (2021). Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge. Genes, 12.","DOI":"10.3390\/genes12060924"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1038\/s41375-024-02368-7","article-title":"Menin inhibitors in pediatric acute leukemia: A comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community","volume":"38","author":"Cuglievan","year":"2024","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1038\/s41375-021-01309-y","article-title":"Therapeutic implications of menin inhibition in acute leukemias","volume":"35","author":"Issa","year":"2021","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1158\/2643-3230.BCD-21-0049","article-title":"Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators","volume":"2","author":"Fornerod","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood.2024027904","article-title":"Diagnosis and Management of AML in Pediatric Patients: Consensus Recommendations from an International Expert Panel","volume":"147","author":"Zwaan","year":"2025","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s12185-023-03533-x","article-title":"Comprehensive molecular understanding of pediatric acute myeloid leukemia","volume":"117","author":"Shiba","year":"2023","journal-title":"Int. J. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41375-023-01877-1","article-title":"The KMT2A recombinome of acute leukemias in 2023","volume":"37","author":"Meyer","year":"2023","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/cam4.5026","article-title":"Mutational landscape and clinical outcome of pediatric acute myeloid leukemia with 11q23\/KMT2A rearrangements","volume":"12","author":"Yuen","year":"2023","journal-title":"Cancer Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1182\/blood-2009-04-215152","article-title":"Novel prognostic subgroups in childhood 11q23\/MLL-rearranged acute myeloid leukemia: Results of an international retrospective study","volume":"114","author":"Balgobind","year":"2009","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.3324\/haematol.2022.281653","article-title":"Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia","volume":"108","author":"Bertrums","year":"2023","journal-title":"Haematologica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1186\/s40001-024-02042-9","article-title":"Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia","volume":"29","author":"Zhang","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/ng.3772","article-title":"Pediatric non\u2013Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes","volume":"49","author":"Branstetter","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/gcc.22538","article-title":"Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: Data from Nordic Society for Pediatric Hematology and Oncology (NOPHO-AML) and review of the literature","volume":"57","author":"Espersen","year":"2018","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1080\/0284186X.2022.2025611","article-title":"MECOM gene overexpression in pediatric patients with acute myeloid leukemia","volume":"61","author":"Elsherif","year":"2022","journal-title":"Acta Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1182\/blood-2021-147576","article-title":"Significant Improvements in Survival for Patients with t(6;9)(p23;q34)\/DEK-NUP214 in Contemporary Trials with Intensification of Therapy: A Report from the Children\u2019s Oncology","volume":"138","author":"Tarlock","year":"2021","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.5045\/br.2020.2020127","article-title":"Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era","volume":"55","author":"Choi","year":"2020","journal-title":"Blood Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/gcc.23110","article-title":"UBTF-internal tandem duplication as a novel poor prognostic factor in pediatric acute myeloid leukemia","volume":"62","author":"Kaburagi","year":"2023","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1182\/blood.2023021359","article-title":"Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors","volume":"143","author":"Barajas","year":"2024","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1182\/blood-2006-10-051342","article-title":"Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: An international retrospective study","volume":"109","author":"Hasle","year":"2007","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/leu.2011.31","article-title":"Prevalence and clinical implications of NRAS mutations in childhood AML: A report from the Children\u2019s Oncology Group","volume":"25","author":"Berman","year":"2011","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1609128","DOI":"10.1155\/2019\/1609128","article-title":"Mutated WT1, FLT3-ITD, and NUP98-NSD1 Fusion in Various Combinations Define a Poor Prognostic Group in Pediatric Acute Myeloid Leukemia","volume":"2019","author":"Niktoreh","year":"2019","journal-title":"J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nm.4439","article-title":"The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions","volume":"24","author":"Bolouri","year":"2018","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3324\/haematol.2025.288481","article-title":"Age-specific mutation profiles and their prognostic implications in pediatric KMT2A-rearranged acute myeloid leukemia","volume":"111","author":"Shoji","year":"2026","journal-title":"Haematologica"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10555-020-09846-1","article-title":"The genomics of acute myeloid leukemia in children","volume":"39","author":"Conneely","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Guarnera, L., D\u2019Addona, M., Bravo-Perez, C., and Visconte, V. (2024). KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25169023"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1200\/JCO.2009.25.6321","article-title":"Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98","volume":"28","author":"Reinhardt","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1182\/bloodadvances.2019000404","article-title":"Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia","volume":"3","author":"Shiba","year":"2019","journal-title":"Blood Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1200\/JCO.24.00826","article-title":"Menin Inhibition with Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)","volume":"43","author":"Issa","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tregnago, C., Benetton, M., Da Ros, A., Borella, G., Longo, G., Polato, K., Francescato, S., Biffi, A., and Pigazzi, M. (2021). Novel Compounds Synergize with Venetoclax to Target KMT2A-Rearranged Pediatric Acute Myeloid Leukemia. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.820191"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1182\/bloodadvances.2023012041","article-title":"Venetoclax: A new player in the treatment of children with high-risk myeloid malignancies?","volume":"8","author":"Masetti","year":"2024","journal-title":"Blood Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1182\/blood.2025029391","article-title":"FLAG-IDA plus venetoclax for children, adolescents, and young adults with newly diagnosed AML","volume":"146","author":"Raj","year":"2025","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Adriaanse, F.R.S., Schneider, P., Arentsen-Peters, S., Fonseca, A., Stutterheim, J., Pieters, R., Zwaan, C.M., and Stam, R.W. (2024). Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116020"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Fedorov, K., Maiti, A., and Konopleva, M. (2023). Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions. Cancers, 15.","DOI":"10.3390\/cancers15082312"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s11864-022-00952-6","article-title":"Which FLT3 Inhibitor for Treatment of AML?","volume":"23","author":"Senapati","year":"2022","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1182\/bloodadvances.2019000919","article-title":"Gilteritinib is a clinically active FLT3 inhibitor with broad activity against FLT3 kinase domain mutations","volume":"4","author":"Tarver","year":"2020","journal-title":"Blood Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1038\/s41375-021-01148-x","article-title":"Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: Long-term follow-up of the randomized controlled SORAML trial","volume":"35","author":"Serve","year":"2021","journal-title":"Leukemia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1182\/blood-2023-187465","article-title":"Characteristics of FLT3-ITD and Efficacy of Sorafenib Treatment in Pediatric AML: A Report from AML-BFM Study Group","volume":"142","author":"Antoniou","year":"2023","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41375-022-01742-7","article-title":"Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: A study from the French AML Intergroup ALFA\/FILO","volume":"37","author":"Dumas","year":"2023","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1182\/bloodadvances.2021005164","article-title":"Gilteritinib combination therapies in pediatric patients with FLT3-mutated acute myeloid leukemia","volume":"5","author":"McCall","year":"2021","journal-title":"Blood Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1182\/bloodadvances.2025017738","article-title":"Quizartinib for patients with newly diagnosed FLT3-ITD-positive AML who received maintenance therapy in QuANTUM-First","volume":"10","author":"Levis","year":"2026","journal-title":"Blood Adv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1200\/JCO-25-01841","article-title":"Quizartinib for Newly Diagnosed FLT3-ITD-Negative Acute Myeloid Leukemia: The Randomized, Double-Blind, Placebo-Controlled, Phase 2 QUIWI Study","volume":"44","author":"Montesinos","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1182\/blood-2024-204779","article-title":"Final Results of Quiwi: A Double Blinded, Randomized Pethema Trial Comparing Standard Chemotherapy Plus Quizartinib Versus Placebo in Adult Patients with Newly Diagnosed FLT3-ITD Negative AML","volume":"144","author":"Montesinos","year":"2024","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood-2023-181792","article-title":"Chip-AML22 Master Protocol: An Open-Label Clinical Trial in Newly Diagnosed Pediatric De Novo Acute Myeloid Leukemia (AML) Patients Including a Linked Phase II Trial with Quizartinib in FLT3-ITD\/NPM1wt Patients\u2014A Study By the NOPHO-DB-SHIP Consortium","volume":"142","author":"Kaspers","year":"2023","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1182\/blood-2019-121736","article-title":"A Phase 1\/2 Study of Quizartinib (Q) in Combination with Re-Induction Chemotherapy and as Single-Agent Continuation Therapy in Pediatric and Young Adult Patients with Relapsed\/Refractory (R\/R) -ITD Acute Myeloid Leukemia (AML)","volume":"134","author":"Zwaan","year":"2019","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/leu.2016.361","article-title":"NUP98-fusion transcripts characterize different biological entities within acute myeloid leukemia: A report from the AIEOP-AML group","volume":"31","author":"Bisio","year":"2017","journal-title":"Leukemia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.ccell.2016.10.019","article-title":"NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis","volume":"30","author":"Xu","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1182\/blood-2014-04-570929","article-title":"NUP98\/NSD1 and FLT3\/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: A COG and SWOG report","volume":"124","author":"Ostronoff","year":"2014","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70013","DOI":"10.1002\/hem3.70013","article-title":"NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities","volume":"8","author":"Rasouli","year":"2024","journal-title":"Hemasphere"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1158\/2643-3230.BCD-21-0160","article-title":"Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia","volume":"3","author":"Umeda","year":"2022","journal-title":"Blood Cancer Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bjh.15725","article-title":"CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity","volume":"184","author":"Masetti","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.ccr.2012.10.007","article-title":"An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia","volume":"22","author":"Gruber","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-017-0396-0","article-title":"Hh\/Gli antagonist in acute myeloid leukemia with CBFA2T3-GLIS2 fusion gene","volume":"10","author":"Masetti","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5933","DOI":"10.1182\/bloodadvances.2022008503","article-title":"Targeting FOLR1 in high-risk CBF2AT3-GLIS2 pediatric AML with STRO-002 FOLR1\u2013antibody-drug conjugate","volume":"6","author":"Tang","year":"2022","journal-title":"Blood Adv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e157101","DOI":"10.1172\/JCI157101","article-title":"CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target","volume":"132","author":"Le","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1101\/gad.1393106","article-title":"MOZ is essential for maintenance of hematopoietic stem cells","volume":"20","author":"Katsumoto","year":"2006","journal-title":"Genes Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1158\/2159-8290.CD-24-1517","article-title":"Catalytic inhibition of KAT6\/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia","volume":"15","author":"Gordon","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13045-024-01610-0","article-title":"The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency","volume":"17","author":"Sheridan","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"BSR20220489","DOI":"10.1042\/BSR20220489","article-title":"Mechanisms associated with t(7;12) acute myeloid leukaemia: From genetics to potential treatment targets","volume":"43","author":"Ragusa","year":"2023","journal-title":"Biosci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1038\/s41375-025-02680-w","article-title":"DNA demethylation-mediated downregulation of MNX1 in acute myeloid leukemia","volume":"39","author":"Kelekci","year":"2025","journal-title":"Leukemia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1182\/blood.2019003701","article-title":"Atypical 3q26\/MECOM rearrangements genocopy inv(3)\/t(3;3) in acute myeloid leukemia","volume":"136","author":"Ottema","year":"2020","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/leu.2010.47","article-title":"EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia","volume":"24","author":"Balgobind","year":"2010","journal-title":"Leukemia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/bjh.12444","article-title":"High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: A report from the children\u2019s oncology group","volume":"162","author":"Ho","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41375-025-02842-w","article-title":"BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML","volume":"40","author":"Birdwell","year":"2025","journal-title":"Leukemia"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"865","DOI":"10.3324\/haematol.2013.098517","article-title":"t(6;9)(p22;q34)\/DEK-NUP214-rearranged pediatric myeloid leukemia: An international study of 62 patients","volume":"99","author":"Sandahl","year":"2014","journal-title":"Haematologica"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/sj.leu.2404233","article-title":"A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare \u2018poor prognosis\u2019 myeloid malignancies","volume":"20","author":"Slovak","year":"2006","journal-title":"Leukemia"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/MOP.0000000000000981","article-title":"Targeting the Ras pathway in pediatric hematologic malignancies","volume":"33","author":"Pikman","year":"2021","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"726","DOI":"10.21037\/tp-20-102","article-title":"Influence of KIT mutations on prognosis of pediatric patients with core-binding factor acute myeloid leukemia: A systematic review and meta-analysis","volume":"9","author":"Fan","year":"2020","journal-title":"Transl. Pediatr."},{"key":"ref_72","unstructured":"National Comprehensive Cancer Network (2024). Acute Myeloid Leukemia, National Comprehensive Cancer Network."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Xu, H., Wen, Y., Jin, R., and Chen, H. (2022). Epigenetic modifications and targeted therapy in pediatric acute myeloid leukemia. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.975819"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.3324\/haematol.2013.094565","article-title":"Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia","volume":"99","author":"Valerio","year":"2014","journal-title":"Haematologica"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13148-017-0411-x","article-title":"A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML","volume":"9","author":"Gore","year":"2017","journal-title":"Clin. Epigenet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1182\/blood-2025-3446","article-title":"Epigenetic priming improves survival for pediatric Acute Myeloid Leukemia: Results from the multicenter randomized AML16 trial","volume":"146","author":"Gruber","year":"2025","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1182\/blood-2024-205666","article-title":"A Phase 3 Randomized Trial for Patients with De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 with GO\u2014A Report from the Children\u2019s Oncology Group","volume":"144","author":"Pollard","year":"2024","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/leu.2009.30","article-title":"Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: Results of the St Jude AML97 trial","volume":"23","author":"Rubnitz","year":"2009","journal-title":"Leukemia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/ajh.26601","article-title":"Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed acute myeloid leukemia","volume":"97","author":"DiNardo","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1111\/bjh.18844","article-title":"Efficacy and safety of FLAG-IDA as front-line therapy in de novo paediatric acute myeloid leukaemia population","volume":"202","author":"Doan","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1182\/blood-2021-147379","article-title":"Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Collaboration","volume":"138","author":"Trabal","year":"2021","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1182\/blood-2024-194827","article-title":"Phase 1 Results: First-in-Human Phase 1\/2 Study of the Menin-MLL Inhibitor Enzomenib (DSP-5336) in Patients with Relapsed or Refractory Acute Leukemia","volume":"144","author":"Zeidner","year":"2024","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1182\/blood-2024-207106","article-title":"Bleximenib Dose Optimization and Determination of RP2D from a Phase 1 Study in Relapsed\/Refractory Acute Leukemia Patients with and Alterations","volume":"144","author":"Searle","year":"2024","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1182\/blood-2024-204375","article-title":"Phase I\/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine\/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R\/R AML","volume":"144","author":"Issa","year":"2024","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1182\/blood-2024-199170","article-title":"Ziftomenib Combined with Venetoclax\/Azacitidine in Relapsed\/Refractory or Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007","volume":"144","author":"Fathi","year":"2024","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/ejh.14383","article-title":"Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies","volume":"114","author":"Bruzzese","year":"2025","journal-title":"Eur. J. Haematol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S1470-2045(18)30240-7","article-title":"Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: An open-label, multicentre, single-arm, phase 2 trial","volume":"19","author":"Cortes","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1002\/ajh.26142","article-title":"Differentiation syndrome with lower-intensity treatments for acute myeloid leukemia","volume":"96","author":"Fathi","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1182\/blood.2024024008","article-title":"How I treat acute myeloid leukemia with differentiation therapy","volume":"145","author":"Issa","year":"2025","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1182\/blood-2023-187642","article-title":"First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors","volume":"142","author":"Dutta","year":"2023","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Uckun, F.M., Lin, T.L., Mims, A.S., Patel, P., Lee, C., Shahidzadeh, A., Shami, P.J., Cull, E., Cogle, C.R., and Watts, J. (2021). A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed\/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Cancers, 13.","DOI":"10.3390\/cancers13164113"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1182\/blood-2022-167468","article-title":"Updated Results from a Phase 1 Study of APVO436, a Novel Bispecific Anti-CD123 x Anti-CD3 Adaptir T Molecule, in Relapsed\/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome","volume":"140","author":"Watts","year":"2022","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1016\/j.ymthe.2023.05.009","article-title":"Chimeric TIM-4 receptor-modified T cells targeting phosphatidylserine mediates both cytotoxic anti-tumor responses and phagocytic uptake of tumor-associated antigen for T cell cross-presentation","volume":"31","author":"Cieniewicz","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1182\/blood-2024-198686","article-title":"Phase 2a Study of SLS009, a Highly Selective CDK9 Inhibitor, in Combination with Azacitidine and Venetoclax for Relapsed\/Refractory Acute Myeloid Leukemia after Prior Venetoclax Treatment","volume":"144","author":"Zeidner","year":"2024","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1200\/JCO.2025.43.16_suppl.2606","article-title":"A phase 1b\/2, open-label study of selective Axl, Mer and CSF1R inhibitor adrixetinib (Q702) in combination with intravenous pembrolizumab in patients with selected advanced solid tumors: Results of a phase 1 study (QRNT-008)","volume":"43","author":"Chon","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1182\/blood-2022-167972","article-title":"A Phase 1\/2 Dose Escalation Study of the Myeloid Kinase Inhibitor HM43239 in Patients with Relapsed or Refractory Acute Myeloid Leukemia","volume":"140","author":"Daver","year":"2022","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/pds.4975","article-title":"Real-world evidence to support regulatory decision-making for medicines: Considerations for external control arms","volume":"29","author":"Burcu","year":"2020","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e2530277","DOI":"10.1001\/jamanetworkopen.2025.30277","article-title":"Design, Conduct, and Analysis of Externally Controlled Trials","volume":"8","author":"Liu","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1182\/blood-2023-172422","article-title":"A First-in-Human Phase 1 Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Adult Patients with Relapsed\/Refractory Acute Leukemia Harboring KMT2A or NPM1 Alterations","volume":"142","author":"Jabbour","year":"2023","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5199","DOI":"10.1182\/blood-2025-5199","article-title":"Bleximenib in combination with intensive chemotherapy: A phase 1b study in newly diagnosed Acute Myeloid Leukemia with KMT2A or NPM1 alterations","volume":"146","author":"Schuh","year":"2025","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1182\/blood-2025-47","article-title":"Phase II Study of the all-oral combination of revumenib (SNDX-5613) with decitabine\/cedazuridine (ASTX727) and venetoclax (SAVE) in newly diagnosed AML","volume":"146","author":"Jen","year":"2025","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1182\/blood-2025-877","article-title":"Etoposide can be safely removed from induction chemotherapy without impacting survival for pediatric acute myeloid leukemia\u2014A report from the Children\u2019s oncology group study AAML1831","volume":"146","author":"Rossoff","year":"2025","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"10546","DOI":"10.1200\/JCO.2017.35.15_suppl.10546","article-title":"Phase I study of pexidartinib (PLX3397) in children with refractory leukemias and solid tumors including neurofibromatosis type I (NF1) related plexiform neurofibromas (PN)","volume":"35","author":"Hittson","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1182\/blood-2025-1656","article-title":"ITCC-101\/APAL2020D: A randomized Phase 3 trial of fludarabine\/cytarabine\/gemtuzumab ozogamycin with or without venetoclax in children with relapsed Acute Myeloid Leukemia","volume":"146","author":"Ishimaru","year":"2025","journal-title":"Blood"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1182\/blood-2024-207197","article-title":"Unleashing the Power of CD19 CAR-T in Relapsed AML: Findings from a Prospective Single-Center Clinical Trial","volume":"144","author":"Yin","year":"2024","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1182\/blood-2023-181593","article-title":"Outcomes for Children with High Risk Acute Myeloid Leukemia on the Myechild 01 International Phase III Clinical Trial","volume":"142","author":"Moore","year":"2023","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.1200\/JCO.2021.39.15_suppl.7010","article-title":"Phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS)","volume":"39","author":"Venugopal","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1182\/blood-2025-932","article-title":"Preliminary safety and efficacy of myeloablative orca-q with tacrolimus or without graft-versus-host disease prophylaxis for treatment of advanced hematologic malignancies","volume":"146","author":"Srour","year":"2025","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41409-024-02347-7","article-title":"The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians\u2014Oral Session (O009-O154)","volume":"59","author":"Shouval","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41588-023-01640-3","article-title":"A new genomic framework to categorize pediatric acute myeloid leukemia","volume":"56","author":"Umeda","year":"2024","journal-title":"Nat. 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