{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:01:47Z","timestamp":1792026107128,"version":"4.4.0"},"reference-count":278,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NIH\/National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL151390"],"award-info":[{"award-number":["R01HL151390"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NIH\/National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R56HL169348"],"award-info":[{"award-number":["R56HL169348"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NIH\/National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA285400"],"award-info":[{"award-number":["R01CA285400"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/National Institute of Aging","award":["RF1AG093995"],"award-info":[{"award-number":["RF1AG093995"]}]},{"name":"Blood Cancer United, formerly the Leukemia and Lymphoma Society (LLS), Scholar Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is a biologically heterogeneous and clinically aggressive hematologic malignancy defined by the clonal expansion of immature myeloid progenitors, resulting in progressive bone marrow (BM) failure, peripheral cytopenias, and fatal infectious or hemorrhagic sequelae. The adverse clinical outcomes associated with AML arise from the combined effects of disrupted physiological hematopoiesis, persistence of therapy-refractory leukemic stem cells (LSCs), and extensive inter- and intratumoral genetic and epigenetic heterogeneity that underlies rapid disease progression and relapse. AML constitutes a prototypical disorder of hematopoietic dysregulation, wherein aberrant self-renewal capacity and arrested differentiation programs drive malignant transformation through the integrated influence of recurrent genomic lesions, epigenetic reprogramming, metabolic alterations, dysregulated signaling cascades, and reciprocal interactions with the BM microenvironment. These processes collectively reconfigure transcriptional landscapes and cellular hierarchies within the leukemic compartment. The objectives of this review are to provide an integrated framework for understanding AML pathobiology encompassing chromosomal abnormalities, transcriptional and epigenetic regulatory networks, and microenvironmental cues and to emphasize emerging analytical paradigms, including integrative multi-omics, single-cell and spatial technologies, and system-level approaches, which are reshaping conceptual models of malignant hematopoiesis and accelerating the development of mechanism-based therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells15040338","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:52:21Z","timestamp":1770979941000},"page":"338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inside the Battle Against Acute Myeloid Leukemia: Biology, Breakthroughs, and Hope"],"prefix":"10.3390","volume":"15","author":[{"given":"Jiayang","family":"Bao","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA"},{"name":"UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Freund","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA"},{"name":"UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Sund","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA"},{"name":"UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-537X","authenticated-orcid":false,"given":"Wei","family":"Du","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA"},{"name":"UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature20598","article-title":"A 17-gene stemness score for rapid determination of risk in acute leukaemia","volume":"540","author":"Ng","year":"2016","journal-title":"Nature"},{"key":"ref_2","first-page":"107","article-title":"The global epidemiology of acute myeloid leukaemia","volume":"23","author":"Bewersdorf","year":"2025","journal-title":"Nat. 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