{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:03:07Z","timestamp":1791489787709,"version":"4.3.4"},"reference-count":91,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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>Background\/Objectives: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with historically poor outcomes, particularly among older adults and patients harboring high-risk molecular features. Advances in genomic profiling have enabled the development of targeted therapies, reshaping treatment algorithms beyond conventional cytarabine-anthracycline induction and hypomethylating agent-based regimens. This review summarizes current evidence and emerging therapeutic strategies across four evolving areas: menin inhibition, FLT3 inhibition, IDH inhibition and treatment approaches for TP53-mutated AML. Methods: We reviewed published clinical trials, preclinical studies, and ongoing clinical trials evaluating targeted therapies in AML. Emphasis was placed on agents with regulatory approval or substantial clinical development, including menin inhibitors, FLT3 inhibitors, IDH inhibitors and novel therapies directed at TP53-mutated disease. Mechanistic data, response rates, survival outcomes, and resistance patterns were analyzed to provide an updated overview of therapeutic progress. Results: Menin inhibitors have demonstrated significant activity in NPM1-mutated and KMT2A-rearranged AML, with agents such as revumenib and ziftomenib producing meaningful remission rates and ongoing studies exploring combination strategies to mitigate resistance. FLT3 inhibitors, including midostaurin, gilteritinib, and quizartinib, have improved survival in FLT3-mutated AML, while emerging evidence supports potential benefit in selected FLT3\u2013wild-type disease based on FLT3-like gene expression signatures. IDH inhibitors, namely ivosidenib and enasidenib, have provided increased efficacy in AML patients carrying these mutations. Questions still remain regarding their efficacy in contrast to venetoclax which has been shown to be particularly effective against this population. In contrast, TP53-mutated AML remains a therapeutic challenge: although hypomethylating-agent\/venetoclax-based regimens yield improved initial responses, remissions are generally short-lived and overall survival remains poor. Early-phase therapies, including p53 reactivators and multi-kinase inhibitors, show preclinical promise but lack definitive clinical efficacy to date. Conclusions: Targeted therapies have improved outcomes in molecularly defined subsets of AML, with menin, IDH and FLT3 inhibitors representing major advances. However, TP53-mutated AML continues to carry a dismal prognosis, underscoring the need for more effective therapeutic strategies. Continued biomarker-driven research, novel drug combinations, and mechanistic insights will be essential to further refine AML treatment and improve long-term survival across disease subsets.<\/jats:p>","DOI":"10.3390\/cancers18040659","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:50:30Z","timestamp":1771401030000},"page":"659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Management of Acute Myeloid Leukemia: A Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Chetan","family":"Jeurkar","sequence":"first","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3134-8652","authenticated-orcid":false,"given":"Lana","family":"King","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4887-0762","authenticated-orcid":false,"given":"David","family":"Baek","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Wilde","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Keiffer","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-744X","authenticated-orcid":false,"given":"Margaret","family":"Kasner","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","unstructured":"SEER Database (2025). Cancer Stat Facts: Leukemia\u2014Acute Myeloid Leukemia, National Cancer Institute."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1136\/bmj.1.5846.131","article-title":"Management of Adult Acute Myelogenous Leukaemia","volume":"1","author":"Crowther","year":"1973","journal-title":"Br. Med. J."},{"key":"ref_3","first-page":"2685","article-title":"CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients with Newly Diagnosed Secondary Acute Myeloid Leukemia","volume":"36","author":"Lancet","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"617","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":"ref_5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1182\/blood.2024026232","article-title":"Menin inhibitors in the treatment of acute myeloid leukemia","volume":"145","author":"Huls","year":"2025","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ccr.2008.05.003","article-title":"Menin critically links MLL proteins with LEDGF on cancer-associated target genes","volume":"14","author":"Yokoyama","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_7","doi-asserted-by":"crossref","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":"ref_8","doi-asserted-by":"crossref","unstructured":"Niscola, P., Gianfelici, V., Giovannini, M., Piccioni, D., Mazzone, C., and Fabritiis, P. (2025). Menin Inhibitors: New Targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias. Cancers, 17.","DOI":"10.3390\/cancers17010142"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41408-021-00557-6","article-title":"Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements","volume":"11","author":"Issa","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/S1470-2045(24)00386-3","article-title":"Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): A multicentre, open-label, multi-cohort, phase 1 trial","volume":"25","author":"Wang","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","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_14","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1182\/blood.2023022480","article-title":"Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias","volume":"144","author":"Kwon","year":"2024","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/s41586-023-05755-9","article-title":"MEN1 mutations mediate clinical resistance to menin inhibition","volume":"615","author":"Perner","year":"2023","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"216","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_17","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1172\/JCI129126","article-title":"Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia","volume":"130","author":"Klossowski","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12935-023-02877-y","article-title":"A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1","volume":"23","author":"Numata","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117788","DOI":"10.1016\/j.biopha.2024.117788","article-title":"Targeting FMS-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia: Novel molecular approaches and therapeutic challenges","volume":"182","author":"Rataj","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.4081\/oncol.2012.e8","article-title":"An overview on the role of FLT3-tyrosine kinase receptor in acute myeloid leukemia: Biology and treatment","volume":"6","author":"Grafone","year":"2012","journal-title":"Oncol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/sj.leu.2400812","article-title":"Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines","volume":"11","author":"Yokota","year":"1997","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood-2002-02-0492","article-title":"The roles of FLT3 in hematopoiesis and leukemia","volume":"100","author":"Gilliland","year":"2002","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41375-018-0357-9","article-title":"Targeting FLT3 mutations in AML: Review of current knowledge and evidence","volume":"33","author":"Daver","year":"2019","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1182\/blood.V98.6.1752","article-title":"The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: Analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials","volume":"98","author":"Kottaridis","year":"2001","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2209","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":"ref_26","doi-asserted-by":"crossref","first-page":"e35813","DOI":"10.1002\/cncr.35813","article-title":"A retrospective study of outcomes across time and treatment regimens in newly diagnosed, FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia","volume":"131","author":"Bazinet","year":"2025","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1056\/NEJMoa1614359","article-title":"Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation","volume":"377","author":"Stone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1056\/NEJMoa1902688","article-title":"Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML","volume":"381","author":"Perl","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1182\/blood-2024-201595","article-title":"Gilteritinib Results in Higher Remission and Transplant Rates Than Midostaurin but Does Not Increase the Post-Induction Mutational MRD Negative Rate: Results of the Phase 2 Randomized Precog 0905 Study in Newly Diagnosed FLT3 Mutated AML","volume":"144","author":"Luger","year":"2024","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1200\/JCO.23.01911","article-title":"Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory FLT3-Mutated AML","volume":"42","author":"Short","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/S0140-6736(23)00464-6","article-title":"Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Erba","year":"2023","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6191","DOI":"10.1182\/blood-2022-170445","article-title":"Bmf-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML","volume":"140","author":"Law","year":"2022","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.1182\/blood-2023-174745","article-title":"STI-8591, a Novel Tyrosine Kinase Inhibitor, Shows Excellent Antileukemic Activity in FLT3-Mutated (mut) Acute Myeloid Leukemia (AML)","volume":"142","author":"Zhang","year":"2023","journal-title":"Blood"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1182\/blood.V87.3.1089.bloodjournal8731089","article-title":"Expression of the Hematopoietic Growth Factor Receptor FLT3 (STK-1\/Flk2) in Human Leukemias","volume":"87","author":"Carow","year":"1996","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E734771d","DOI":"10.1097\/01.HS9.0000967432.73477.1d","article-title":"S130: Preliminary results of QUIWI: A double blinded, randomized clinical trial comparing standard chemotherapy plus quizartinib versus placebo in adult patients with newly diagnosed FLT3-itd wild-type aml","volume":"7","author":"Montesinos","year":"2023","journal-title":"Hemasphere"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1182\/blood-2023-180482","article-title":"The FLT3-like Gene Expression Signature Predicts Response to Quizartinib in Wild-Type FLT3 Acute Myeloid Leukemia: An Analysis of the Pethema Quiwi Trial","volume":"142","author":"Botella","year":"2023","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1200\/JCO.2013.48.8783","article-title":"Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status","volume":"31","author":"Cortes","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104424","DOI":"10.1016\/j.critrevonc.2024.104424","article-title":"Understanding mechanisms of resistance to FLT3 inhibitors in adult FLT3-mutated acute myeloid leukemia to guide treatment strategy","volume":"201","author":"Ruglioni","year":"2024","journal-title":"Crit. Rev. Oncol.\/Hematol"},{"key":"ref_40","unstructured":"Coleman, W., and Tsongalis, G. (2016). Diagnosic Molecular Pathology, Academic Press."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41408-021-00497-1","article-title":"Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm","volume":"11","author":"Issa","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/ajh.24072","article-title":"Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML","volume":"90","author":"Dinardo","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/ajh.26694","article-title":"Contemporary outcomes in IDH-mutated acute myeloid leukemia: The impact of co-occuring NPM1 mutations and venetoclax-based treatment","volume":"97","author":"Lachowiez","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_44","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":"Dohner","year":"2022","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6126","DOI":"10.1182\/blood-2024-207413","article-title":"Outcomes of adult patients with newly diagnosed IDH-mutated acute myeloid leukemia receiving intensive chemotherapy plus venetoclax","volume":"144","author":"Croden","year":"2024","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1056\/NEJMoa2117344","article-title":"Ivosidenib and azacitidine in IDH-1 muitated acute myeloid leukemia","volume":"386","author":"Montesinos","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/S1470-2045(21)00494-0","article-title":"Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): A single-arm, phase 1b and randomised, phase 2 trial","volume":"22","author":"DiNardo","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1016\/S2352-3026(22)00292-7","article-title":"Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: Phase 1 results of a phase \u00bd trial","volume":"10","author":"Watts","year":"2023","journal-title":"Lancet Hematol."},{"key":"ref_49","unstructured":"(2026, February 05). NCT05401097. IDH Targeted\/Non-Targeterd vs Non-Targeted\/IDH-Targeted Approaches in the Treatment of Newly Diagnosed IDH-mutated AML Patients Not Candidates for Intensive Induction Therapy (I-DATA Study). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05401097."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e887","DOI":"10.1016\/S2352-3026(25)00254-6","article-title":"Enasidenib plus venetoclax in patients with IDH2-mutated relapsed or refractory acute myeloid leukaemia or myelodysplastic syndrome: A multicentre, single arm, phase 1\/2b trial","volume":"12","author":"Gupta","year":"2025","journal-title":"Lancet Heematol."},{"key":"ref_51","unstructured":"(2026, February 06). NCT03471260. Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients with IDH2 Mutated Hematologic Malignancies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03471260."},{"key":"ref_52","unstructured":"(2026, February 06). NCT04774393. Decitabine\/Cedazuridine and Venetoclax in Combination with Ivosidenib or Enasidenib for the Treatemtn of Relapsed or Refractory Acute Myeloid Leukemia, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04774393."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1021\/acsmedchemlett.4c00625","article-title":"Discovery of HMPL-306 (ranosidenib), a new potent and selective dual inhibitor of mutant IDH1 and 2 in clinical devleopment for cancer treatment","volume":"16","author":"Xiao","year":"2025","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100575","DOI":"10.1016\/j.medj.2025.100575","article-title":"HMPL-306 in relapsed or refractory IDH1 and\/or IDH2-mutated acute myeloid leukemia: A phase 2 study","volume":"6","author":"Hu","year":"2025","journal-title":"Med"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1038\/leu.2017.46","article-title":"Pan-mutant IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo","volume":"31","author":"Chaturvedi","year":"2017","journal-title":"Leukemia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1038\/s41375-020-0996-5","article-title":"Safety and efficacy of BAY1436032 in IDH1-mutant AML: Phase 1 study results","volume":"34","author":"Heuser","year":"2020","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/s41375-019-0582-x","article-title":"In vivo efficacy of mutatnt IDH1 inhibitor HMS-101 and structural resolution of distinct binding site","volume":"34","author":"Chaturvedi","year":"2019","journal-title":"Leukemia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.apsb.2021.03.005","article-title":"Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1182\/blood-2017-02-763086","article-title":"Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: Projections on diagnostic workup and therapy","volume":"130","author":"Prokocimer","year":"2017","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41580-019-0110-x","article-title":"The multiple mechanisms that regulate p53 activity and cell fate","volume":"20","author":"Hafner","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e331","DOI":"10.1038\/bcj.2015.59","article-title":"TP53 mutations in de novo acute myeloid leukemia patients: Longitudinal follow-ups show the mutation is stable during disease evolution","volume":"5","author":"Hou","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41408-024-01186-5","article-title":"What have we learned about TP53-mutated acute myeloid leukemia?","volume":"14","author":"Shahzad","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13045-015-0139-z","article-title":"TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases","volume":"8","author":"Ok","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.hoc.2019.11.004","article-title":"Targeting TP53 mutations in myelodysplastic syndromes","volume":"34","author":"Hunter","year":"2020","journal-title":"Hematol.\/Oncol. Clin."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/leu.2008.375","article-title":"The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia","volume":"23","author":"Seifert","year":"2009","journal-title":"Leukemia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/leu.2015.304","article-title":"Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes","volume":"30","author":"Sallman","year":"2016","journal-title":"Leukemia"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrc.2015.2","article-title":"DNA damage and the balance between survival and death in cancer biology","volume":"16","author":"Roos","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"100671","DOI":"10.1016\/j.drup.2019.100671","article-title":"Towards the overcoming of anticancer drug resistance mediated by p53 mutations","volume":"49","author":"Cao","year":"2020","journal-title":"Drug Resist. Updat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41419-022-05408-1","article-title":"Mutant p53 in cancer: From molecular mechanism to therapeutic modulation","volume":"13","author":"Chen","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/nm0796-811","article-title":"Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients","volume":"2","author":"Aas","year":"1996","journal-title":"Nat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41568-023-00658-3","article-title":"Translating p53-based therapies for cancer into the clinic","volume":"24","author":"Peuget","year":"2024","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41573-022-00571-8","article-title":"Drugging p53 in cancer: One protein, many targets","volume":"22","author":"Hassin","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1038\/s41375-024-02417-1","article-title":"Managing the unmanageable: Evidence-driven approaches to real-world patient prototypes of TP53-mutant myelodysplastic neoplasms and acute myeloid leukemia","volume":"38","author":"Patel","year":"2024","journal-title":"Leukemia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1080\/10428194.2017.1422864","article-title":"Outcomes with lower intensity therapy in TP53-mutated acute myeloid leukemia","volume":"59","author":"Boddu","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1002\/cncr.33689","article-title":"Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax","volume":"127","author":"Kim","year":"2021","journal-title":"Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1002\/cncr.33675","article-title":"Outcomes in patients with newly diagnosed TP53-mutated acute myeloid leukemia with or without venetoclax-based therapy","volume":"127","author":"Venugopal","year":"2021","journal-title":"Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000535628","article-title":"TP53-mutated myelodysplastic syndrome and acute myeloid leukemia: Current guidelines, therapies, and future considerations","volume":"147","author":"DiGennaro","year":"2024","journal-title":"Acta Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1182\/blood.2024024245","article-title":"TP53-mutated acute myeloid leukemia: How can we improve outcomes?","volume":"145","author":"Sallman","year":"2025","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1200\/JCO.20.02341","article-title":"Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant Myelodysplastic Syndromes","volume":"39","author":"Sallman","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_81","unstructured":"Aprea Therapeutics (2021). A Phase III Multicenter, Randomized, Open Label Study of APR-246 in Combination with Azacitidine Versus Azacitidine Alone for the Treatment of (Tumor Protein) TP53 Mutant Myelodysplastic Syndromes, Aprea Therapeutics."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S290","DOI":"10.1016\/S2152-2650(21)01694-3","article-title":"AML-196: The first-in-class anti-CD47 antibody magrolimab in combination with azacitidine is well tolerated and effective in AML patients: Phase 1b results","volume":"21","author":"Sallman","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1182\/blood.2024027408","article-title":"Magrolimab plus azacitidine vs physician\u2019s choice for untreated TP53-mutated acute myeloid leukemia: The ENHANCE-2 study","volume":"146","author":"Zeidner","year":"2025","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"TPS7067","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS7067","article-title":"Lemzoparlimab with venetoclax and\/or azacitidine in patients with acute myeloid leuekmia or myelodysplastic syndromes: A phase 1b dose escalation study","volume":"40","author":"Daver","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1182\/blood.2025028935","article-title":"Restoring p53 wild-type conformation in TP53-Y220C-mutant acute myeloid leukemia","volume":"146","author":"Carter","year":"2025","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"E272","DOI":"10.1016\/S2352-3026(22)00403-3","article-title":"Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: A phase 1, dose-finding and expansion study","volume":"10","author":"Goldberg","year":"2023","journal-title":"Lancet Hematol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Wang, C., Ming Tan, J., Chitkara, N., and Bhatt, S. (2024). TP53 mutation-mediated immune evation in cancer: Mechanissm and theraputic implications. Cancers, 16.","DOI":"10.3390\/cancers16173069"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1182\/blood-2023-185059","article-title":"The Mevalonate Pathway Is a Therapeutic Target in TP53 Mutant Acute Myeloid Leukemia","volume":"142","author":"Skuli","year":"2023","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"TPS6581","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS6581","article-title":"First-in-human study of autologous chimeric engulfment receptor T-cell CER-1236 targeting TIM-4-l in acute myeloid leukemia (CertainT-1)","volume":"43","author":"Maiti","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1182\/bloodadvances.2020002512","article-title":"TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML","volume":"4","author":"Vadakekolathu","year":"2020","journal-title":"Blood Adv."},{"key":"ref_91","unstructured":"Cullinan Therapeutics Inc. (U.S.) (2026, February 12). CLN-049 in Patients with Relapsed\/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (NCT05143996) [Clinical Trial], Available online: https:\/\/clinicaltrials.gov\/study\/NMCT05143996."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/4\/659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:58:14Z","timestamp":1771401494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/4\/659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":91,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cancers18040659"],"URL":"https:\/\/doi.org\/10.3390\/cancers18040659","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]}}}