{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:37:42Z","timestamp":1779255462950,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Acute myeloid leukemia (AML) with RAM immunophenotype is a newly recognized high\u2010risk AML immunophenotypic subcategory characterized by blasts with bright expression of CD56 and weak to absent expression of CD45, HLA\u2010DR, and CD38, as first described by the Children's Oncology Group (COG). The relationship between AML\u2010RAM and other CD56\u2010positive acute leukemias is unclear. The goal of this study is to characterize the clinicopathological characteristics of AML with RAM phenotype and compare them with other CD56 co\u2010expressing acute leukemias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From a multi\u2010institutional search, we identified a total of 160 CD56+ acute leukemia cases, including AML\u2010RAM (<jats:italic>n<\/jats:italic>\u00a0=\u00a028), CD56+ acute undifferentiated leukemia (AUL) (<jats:italic>n<\/jats:italic>\u00a0=\u00a011), CD56+ T\u2010lymphoblastic leukemia (<jats:italic>n<\/jats:italic>\u00a0=\u00a039), and CD56+ AML (<jats:italic>n<\/jats:italic>\u00a0=\u00a081). We compared the clinical and pathologic findings of these groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AML\u2010RAM patients were significantly younger and presented with significantly higher platelet and white blood cell counts and bone marrow (BM) blast percentages when compared to AUL (<jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05) and had higher median BM blast percentages than T\u2010ALL and CD56+ AML groups (both <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Flow cytometry showed significantly brighter expression of CD56 on blasts as compared to other CD56+ AML cases, partial CD34 expression compared to AUL, and AML, weak\u2010to\u2010absent CD38 expression compared to all groups, and absent HLA\u2010DR and terminal deoxynucleotidyl transferase as compared to AUL and T\u2010ALL (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). The frequency of abnormal karyotypes was significantly higher among RAM when compared to all groups (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Next\u2010generation sequencing profiles differed among the leukemia groups, with significant enrichment of <jats:italic>CBFA2T3::GLIS2<\/jats:italic> fusions (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) and <jats:italic>TP53<\/jats:italic> mutations (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) in RAM cases compared to other AML control groups, and <jats:italic>U2AF1<\/jats:italic> (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), serine and arginine\u2010rich splicing factor 2 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), and BCL6 co\u2010repressor (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) mutations compared to AUL. Clinical outcome analysis demonstrated significantly lower 3\u2010year overall survival of the RAM subgroup (36 months) compared to control groups (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We find that AML with RAM phenotype occurs primarily in younger ages, with distinct clinicopathological, immunophenotypic, and mutational presentations, and worse prognosis. This diagnosis should be considered in the clinical differential diagnosis of CD56\u2010positive acute leukemias.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jha2.1052","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T12:38:53Z","timestamp":1734352733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical, immunophenotypic, and genomic findings of acute myeloid leukemia with RAM immunophenotype: Comparison with other CD56\u2010positive acute leukemias"],"prefix":"10.1002","volume":"6","author":[{"given":"Hanan","family":"Hamdan","sequence":"first","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen\u2010Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sa A.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, Division of Pathology\/Lab Medicine The University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-5462","authenticated-orcid":false,"given":"Jacob","family":"Bledsoe","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Children's Hospital (BCH) Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen M.","family":"Chisholm","sequence":"additional","affiliation":[{"name":"Department of Pathology Seattle Children's Hospital Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-3653","authenticated-orcid":false,"given":"Alexa","family":"Siddon","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Ohgami","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah and ARUP Laboratories Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy I.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah and ARUP Laboratories Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Kurzer","sequence":"additional","affiliation":[{"name":"Stanford Health Care Stanford Medicine Children's Health Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Hasserjian","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Arber","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-468X","authenticated-orcid":false,"given":"Adam","family":"Bagg","sequence":"additional","affiliation":[{"name":"Division of Hematopathology Hospital of the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Foucar","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of New Mexico Albuquerque New Mexico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Margolskee","sequence":"additional","affiliation":[{"name":"Department of Pathology The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorottya","family":"Laczko","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine. 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