{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:16:29Z","timestamp":1785428189624,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National University of Medical Sciences","award":["02\/Accts\/NUMS\/18\/3\/2021"],"award-info":[{"award-number":["02\/Accts\/NUMS\/18\/3\/2021"]}]},{"award":["02\/Accts\/NUMS\/18\/3\/2021"],"award-info":[{"award-number":["02\/Accts\/NUMS\/18\/3\/2021"]}],"id":[{"id":"https:\/\/ror.org\/04tj88f69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is a heterogeneous malignancy, with clonal complexity and somatic mutations critically influencing prognosis and treatment. While global genomic profiling efforts have revolutionized AML classification and risk stratification, the molecular landscape in Pakistani patients remains underexplored. Our aim is to perform targeted next-generation sequencing (NGS) for somatic mutational profiling of newly diagnosed AML patients in Pakistan. This prospective study was conducted at the Armed Forces Institute of Pathology, Pakistan, from January 2021 to January 2026. Among 104 patients, 204 somatic variants were identified (mean: 1.96 variants\/patient), predominantly single-nucleotide variants (49.5%). Missense mutations (38.2%) were most common, with enriched transitions (Ti\/Tv: 1.27:1). Frequently mutated genes included TP53 (22.1%), KIT (9.8%), CEBPA (8.8%), and NRAS (5.9%). Cell-signaling genes (30.4%) and tumor suppressor genes (27.0%) were the most affected functional groups. Co-mutation analysis showed clustering led by DNMT3A\u2013IDH1 co-occurrence (\u03c1 \u2248 0.43). DNA-methylation alterations frequently co-occurred with tumor suppressors (OR \u2248 4.6, p = 0.007), transcription factors (OR \u2248 3.9, p = 0.023), and NPM1 (\u03c1 = 0.32). This study provides the first comprehensive genomic map of Pakistani AML patients, revealing unique mutational signatures. The findings lay the groundwork for population-specific precision oncology in low- and middle-income countries.<\/jats:p>","DOI":"10.3390\/ijms27093927","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:26:41Z","timestamp":1777382801000},"page":"3927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Profiling of Acute Myeloid Leukemia in Pakistan: Comprehensive Variant Landscape Revealed by Targeted NGS"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5394-9290","authenticated-orcid":false,"given":"Rafia","family":"Mahmood","sequence":"first","affiliation":[{"name":"Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan"},{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleem Ahmed","family":"Khan","sequence":"additional","affiliation":[{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Ali","sequence":"additional","affiliation":[{"name":"Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan"},{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Sharif","sequence":"additional","affiliation":[{"name":"Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan"},{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Khurshid","sequence":"additional","affiliation":[{"name":"Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan"},{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilshad","family":"Ahmed","sequence":"additional","affiliation":[{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshal","family":"Shahzad","sequence":"additional","affiliation":[{"name":"Islamabad Medical and Dental College, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Saeed","family":"Malik","sequence":"additional","affiliation":[{"name":"Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan"},{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naghmi","family":"Asif","sequence":"additional","affiliation":[{"name":"Islamabad Medical and Dental College, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidrah","family":"Jahangir","sequence":"additional","affiliation":[{"name":"Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan"},{"name":"National University of Medical Sciences, Abid Majeed Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","article-title":"Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges","volume":"36","author":"Shallis","year":"2019","journal-title":"Blood Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/cncr.33458","article-title":"De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017","volume":"127","author":"Sasaki","year":"2021","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41408-021-00425-3","article-title":"Acute myeloid leukemia: Current progress and future directions","volume":"11","author":"Kantarjian","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41586-018-0623-z","article-title":"Functional genomic landscape of acute myeloid leukaemia","volume":"562","author":"Tyner","year":"2018","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40164-020-00161-7","article-title":"Clinical implications of recurrent gene mutations in acute myeloid leukemia","volume":"9","author":"Yu","year":"2020","journal-title":"Exp. 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