{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:17:55Z","timestamp":1781263075842,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The recent fifth edition WHO classification and ICC classification systems have moved further toward genetically defined classifications of acute leukemias. Both now recognize myelodysplasia\u2010related (MR) mutations as defining of MDS\u2010related AML (AML\u2010MR). Acute leukemias of ambiguous lineage (ALAL) are a heterogenous group of acute leukemias characterized by leukemic blasts that either express markers of multiple lineages, mixed phenotype acute leukemia (MPAL), or too few to be assigned a definitive lineage, acute undifferentiated leukemia (AUL). However, the recent classifications are unclear on how ALALs should be categorized in the presence of MR mutations. In short, the current recommendations are to classify cases that are immunophenotypically consistent with ALAL but harbor MR cytogenetics or mutations as AML\u2010MR. Due to their rarity, investigations into the genetic basis of ALAL are limited but show great heterogeneity in their mutational landscapes. Data on the frequencies and significance of MR mutations in ALAL is particularly scant. Our comprehensive review of the literature reporting on the genetic landscapes of MPAL and AUL shows that a significant proportion of MPAL and AUL cases, ~32% and ~59% on average respectively, may harbor one or more mutations in MR genes, with mutations in\n                    <jats:italic>RUNX1<\/jats:italic>\n                    and\n                    <jats:italic>ASXL1<\/jats:italic>\n                    among the most common. Additional research is needed into the clinical, immunophenotypic, and genetic characteristics of ALAL to aid in refining classification and to support therapeutic decision making.\n                  <\/jats:p>","DOI":"10.1111\/ijlh.14529","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T11:49:42Z","timestamp":1752148182000},"page":"512-520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Significance of Myelodysplasia\u2010Related Mutations and the Genetic Landscape of Acute Leukemias of Ambiguous Lineage"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-8025","authenticated-orcid":false,"given":"Timothy J.","family":"Kirtek","sequence":"first","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-3891","authenticated-orcid":false,"given":"Olga K.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2021.03.016"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2024000554"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-020-00170-6"},{"key":"e_1_2_12_7_1","volume-title":"StatPearls","author":"Vakiti A.","year":"2024"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-301713"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1309\/EM7KCQR4GLMHRCX4"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2004.00397.x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133292"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-610543"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26812"},{"key":"e_1_2_12_14_1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues: World Health Organization Classification of Tumours, Revised","author":"Swerdlow S. 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