{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:44:02Z","timestamp":1768563842542,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,13]]},"group-title":"Hematology","reference-count":28,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Recent genomic studies in adult and pediatric acute myeloid leukemia (AML) demonstrated recurrent in-frame tandem duplications (TD) in exon 13 of upstream binding transcription factor (\n                  <jats:italic>UBTF<\/jats:italic>\n                  ). These alterations, which account for ~4.3% of AMLs in childhood and up to 3% in adult AMLs under 60, are subtype-defining and associated with poor outcomes. Here, we provide a comprehensive investigation into the clinicopathological features of\n                  <jats:italic>UBTF<\/jats:italic>\n                  -TD myeloid neoplasms in childhood, including 89 unique pediatric AML and 6 myelodysplastic syndrome (MDS) cases harboring a tandem duplication in exon 13 of\n                  <jats:italic>UBTF<\/jats:italic>\n                  . We demonstrate that\n                  <jats:italic>UBTF-<\/jats:italic>\n                  TD myeloid tumors are associated with dysplastic features, low bone marrow blast infiltration, and low white blood cell count. Furthermore, using bulk and single-cell analyses, we confirm that\n                  <jats:italic>UBTF<\/jats:italic>\n                  -TD is an early and clonal event associated with a distinct transcriptional profile, whereas the acquisition of\n                  <jats:italic>FLT3<\/jats:italic>\n                  or\n                  <jats:italic>WT1<\/jats:italic>\n                  mutations is associated with more stem cell-like programs. Lastly, we report rare duplications within exon 9 of\n                  <jats:italic>UBTF<\/jats:italic>\n                  that phenocopy exon 13 duplications, expanding the spectrum of\n                  <jats:italic>UBTF<\/jats:italic>\n                  alterations in pediatric myeloid tumors. Collectively, we comprehensively characterize pediatric AML and MDS with\n                  <jats:italic>UBTF-<\/jats:italic>\n                  TD and highlight key clinical and pathologic features that distinguish this new entity from other molecular subtypes of AML.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        Largest cohort of pediatric\n                        <jats:italic>UBTF-<\/jats:italic>\n                        TD in myeloid neoplasms reported to date.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Use of single-cell DNA+protein sequencing technology in 3\n                        <jats:italic>UBTF-<\/jats:italic>\n                        TD samples reveals a clonal evaluation pattern characterized by sequential acquisition of\n                        <jats:italic>WT1<\/jats:italic>\n                        and\n                        <jats:italic>FLT3<\/jats:italic>\n                        mutations and a more stem cell-like protein expression pattern.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Pediatric MDS and AML patients with\n                        <jats:italic>UBTF-<\/jats:italic>\n                        TD alterations dysplastic features with an increase erythroid precursors.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Tandem duplications in exon 9 of\n                        <jats:italic>UBTF<\/jats:italic>\n                        represent a rare but functionally equivalent subgroup of\n                        <jats:italic>UBTF-<\/jats:italic>\n                        TD myeloid neoplasms.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Impact Statement<\/jats:title>\n                  <jats:p>\n                    <jats:italic>UBTF<\/jats:italic>\n                    tandem duplications (TD) are subtype-defining genomic alterations in adult and pediatric myeloid neoplasms. Here, we provide a comprehensive characterization of the largest cohort of pediatric\n                    <jats:italic>UBTF<\/jats:italic>\n                    -TD cases to date, including the recognition of additional UBTF alterations that mimic the exon 13 duplications in pediatric AML.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.11.13.23298320","type":"posted-content","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T21:25:11Z","timestamp":1699910711000},"source":"Crossref","is-referenced-by-count":1,"title":["<i>UBTF<\/i>\n                  Tandem Duplications in Pediatric MDS and AML: Implications for Clinical Screening and Diagnosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-5243","authenticated-orcid":false,"given":"Juan M.","family":"Barajas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Umeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisett","family":"Contreras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahsa","family":"Khanlari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-6698","authenticated-orcid":false,"given":"Tamara","family":"Westover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenchen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittney","family":"Otero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Arribas-Layton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherif","family":"Abdelhamed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangchun","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-1036","authenticated-orcid":false,"suffix":"3rd","given":"Melvin E.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-6960","authenticated-orcid":false,"given":"Jeffery M.","family":"Klco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023111607350696000_2023.11.13.23298320v1.1","doi-asserted-by":"crossref","unstructured":"Umeda M , Ma J , Westover T , Ni Y , Song G , Maciaszek J , et al. 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UBTF-Internal tandem duplication as a novel poor prognostic factor in pediatric acute myeloid leukemia. 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