{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:06:38Z","timestamp":1793153198038,"version":"4.5.0"},"reference-count":95,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Takeda"},{"id":[{"id":"https:\/\/ror.org\/04hjbmv12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Amgen"},{"name":"Ascentage"},{"DOI":"10.13039\/100018201","name":"Syndax","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018201","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Acute myeloid leukemia (AML) pathogenesis is deeply rooted in the concept of clonal evolution, in which hematopoietic stem cells experience an initial genetic insult, followed by the sequential acquisition of mutations leading to various disease phenotypes. Through natural selection, a malignant clone can diversify and propagate with time. Aside from clonal evolution, a number of time-honored principles of molecular oncology account for the initiation and maintenance of AML. These principles include loss of heterozygosity, genomic instability, epigenomic disruption, deregulation of signaling pathways, anti-apoptotic mechanisms, and oncogene addiction. Such tenets of cancer biology not only explain AML cellular behavior but also may inform target validation in AML. Herein, we highlight the current state of targeted therapeutics, including the 14 novel agents (beyond 7+3 chemotherapy) approved by the Food and Drug Administration, in the context of these tenets and discuss future prospects by leveraging current knowledge of AML genomics. Such therapeutic concepts, including synthetic lethality, are especially relevant to TP53-mutant AML, as there are no unique therapies that have received regulatory approval for this subset to date. We emphasize the emerging role of single-cell genomics and multi-omics toward better understanding of AML biology and development of future successful AML therapies.<\/jats:p>","DOI":"10.3390\/cancers18142329","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:32:08Z","timestamp":1784514728000},"page":"2329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modern Concepts in Precision Targeting of Acute Myeloid Leukemia Based on Principles of Molecular Oncology"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4290-0645","authenticated-orcid":false,"given":"Robert","family":"Yuan","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Mariano","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5860-8452","authenticated-orcid":false,"given":"David","family":"Cachia","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA 01655, USA"},{"name":"Center for Clinical and Translational Science, UMass Chan Medical School, Worcester, MA 01655, USA"},{"name":"UMass CHIP Clinic, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1548-918X","authenticated-orcid":false,"given":"Talha","family":"Badar","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplant Program, Division of Hematology\/Oncology, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8208-1902","authenticated-orcid":false,"given":"Shyam A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA 01655, USA"},{"name":"Center for Clinical and Translational Science, UMass Chan Medical School, Worcester, MA 01655, USA"},{"name":"UMass CHIP Clinic, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1038\/s41467-020-16399-y","article-title":"Loss of heterozygosity of essential genes represents a widespread class of potential cancer vulnerabilities","volume":"11","author":"Nichols","year":"2020","journal-title":"Nat. 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