{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T08:03:13Z","timestamp":1771401793725,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002957","name":"Technische Universit\u00e4t Dresden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    PRDM16 (PR Domain Containing 16) is a transcription factor that plays a critical role in hematopoietic stem cell maintenance. In acute myeloid leukemia (AML),\n                    <jats:italic>PRDM16<\/jats:italic>\n                    overexpression is linked to specific cytogenetic risk groups and poor prognosis. However, in\n                    <jats:italic>NPM1<\/jats:italic>\n                    -mutated AMLs,\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression varies widely, with no consensus on its prognostic significance. To understand molecular and clinical associations of\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression in this relevant subgroup, we screened 503 adult\n                    <jats:italic>NPM1<\/jats:italic>\n                    -mutant AML patients. High\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression was associated with mutations in\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    (57% vs 22%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD (51% vs 37%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0258), and therefore a higher rate of ELN2022 intermediate-risk (42% vs 26%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01), compared to low\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression. Accordingly,\n                    <jats:italic>PRDM16<\/jats:italic>\n                    overexpression was not associated with clinical outcome in multivariable analysis adjusting for ELN2022 risk in the unselected\n                    <jats:italic>NPM1<\/jats:italic>\n                    -mutant AML cohort. However, within the double-mutant\n                    <jats:italic>NPM1<\/jats:italic>\n                    \/\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD subgroup (n\u2009=\u2009200), low\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression was an independent prognostic factor for longer survival (hazard ratio [95%-CI] 0.467 [0.270\u20130.807];\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006). On a molecular level, low\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression was associated with mutations in epigenetic regulators (\n                    <jats:italic>TET2<\/jats:italic>\n                    ,\n                    <jats:italic>IDH1<\/jats:italic>\n                    \/\n                    <jats:italic>2<\/jats:italic>\n                    ) and increased\n                    <jats:italic>PRDM16<\/jats:italic>\n                    promoter methylation, suggesting impaired TET\/IDH-mediated DNA-demethylation as underlying mechanism. Notably,\n                    <jats:italic>IDH1<\/jats:italic>\n                    R132C and\n                    <jats:italic>IDH2<\/jats:italic>\n                    R140Q alterations particularly contributed to higher\n                    <jats:italic>PRDM16<\/jats:italic>\n                    promoter methylation and reduced expression. These results suggest an association of\n                    <jats:italic>PRDM16<\/jats:italic>\n                    overexpression with the\n                    <jats:italic>NPM1<\/jats:italic>\n                    \/\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD\/\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    triple-mutant AML genotype, typically linked to high leukemia stem cell frequencies and poor prognosis. Importantly, within this adverse AML subtype low\n                    <jats:italic>PRDM16<\/jats:italic>\n                    expression is an independent prognostic marker for favorable outcome, supporting an anti-leukemic mechanism in AMLs with repressed\n                    <jats:italic>PRDM16<\/jats:italic>\n                    transcription.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-06767-x","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T01:52:10Z","timestamp":1769046730000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PRDM16 expression is an independent prognostic factor in AML with the double-mutant NPM1\/FLT3-ITD genotype"],"prefix":"10.1007","volume":"105","author":[{"given":"Sebastian","family":"Stasik","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Niklas","family":"Eckardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"R\u00f6llig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia D.","family":"Baldus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"Serve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Sch\u00e4fer-Eckart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan W.","family":"Krause","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"H\u00e4nel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Ehninger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Platzbecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bornh\u00e4user","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Schetelig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M.","family":"Middeke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Thiede","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"issue":"3","key":"6767_CR1","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1002\/ajh.26822","volume":"98","author":"S Shimony","year":"2023","unstructured":"Shimony S, Stahl M, Stone RM (2023) Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol 98(3):502\u2013526. https:\/\/doi.org\/10.1002\/ajh.26822","journal-title":"Am J Hematol"},{"issue":"2","key":"6767_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00425-3","volume":"11","author":"H Kantarjian","year":"2021","unstructured":"Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, Garcia-Manero G, Konopleva M, Ravandi F (2021) Acute myeloid leukemia: current progress and future directions. Blood Cancer J 11(2):41. https:\/\/doi.org\/10.1038\/s41408-021-00425-3","journal-title":"Blood Cancer J"},{"issue":"2","key":"6767_CR3","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3324\/haematol.2022.280800","volume":"108","author":"P Stelmach","year":"2023","unstructured":"Stelmach P, Trumpp A (2023) Leukemic stem cells and therapy resistance in acute myeloid leukemia. Haematologica 108(2):353\u2013366. https:\/\/doi.org\/10.3324\/haematol.2022.280800","journal-title":"Haematologica"},{"issue":"50","key":"6767_CR4","doi-asserted-by":"publisher","first-page":"31945","DOI":"10.1073\/pnas.2017626117","volume":"117","author":"KO Gudmundsson","year":"2020","unstructured":"Gudmundsson KO, Nguyen N, Oakley K, Han Y, Gudmundsdottir B, Liu P, Tessarollo L, Jenkins NA, Copeland NG, Du Y (2020) Prdm16 is a critical regulator of adult long-term hematopoietic stem cell quiescence. Proc Natl Acad Sci U S A 117(50):31945\u201331953. https:\/\/doi.org\/10.1073\/pnas.2017626117","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"6767_CR5","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1038\/ncb2101","volume":"12","author":"S Chuikov","year":"2010","unstructured":"Chuikov S, Levi BP, Smith ML, Morrison SJ (2010) Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress. Nat Cell Biol 12(10):999\u20131006. https:\/\/doi.org\/10.1038\/ncb2101","journal-title":"Nat Cell Biol"},{"issue":"19","key":"6767_CR6","doi-asserted-by":"publisher","first-page":"5057","DOI":"10.1182\/blood-2010-08-300145","volume":"117","author":"F Aguilo","year":"2011","unstructured":"Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW (2011) Prdm16 is a physiologic regulator of hematopoietic stem cells. Blood 117(19):5057\u20135066. https:\/\/doi.org\/10.1182\/blood-2010-08-300145","journal-title":"Blood"},{"issue":"1","key":"6767_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.tem.2015.11.005","volume":"27","author":"J Chi","year":"2016","unstructured":"Chi J, Cohen P (2016) The multifaceted roles of PRDM16: adipose biology and beyond. Trends Endocrinol Metab 27(1):11\u201323. https:\/\/doi.org\/10.1016\/j.tem.2015.11.005","journal-title":"Trends Endocrinol Metab"},{"issue":"1","key":"6767_CR8","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cmet.2007.06.001","volume":"6","author":"P Seale","year":"2007","unstructured":"Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6(1):38\u201354. https:\/\/doi.org\/10.1016\/j.cmet.2007.06.001","journal-title":"Cell Metab"},{"issue":"2","key":"6767_CR9","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.molcel.2016.03.010","volume":"62","author":"B Zhou","year":"2016","unstructured":"Zhou B, Wang J, Lee SY, Xiong J, Bhanu N, Guo Q, Ma P, Sun Y, Rao RC, Garcia BA, Hess JL, Dou Y (2016) PRDM16 suppresses MLL1r leukemia via intrinsic histone methyltransferase activity. Mol Cell 62(2):222\u2013236. https:\/\/doi.org\/10.1016\/j.molcel.2016.03.010","journal-title":"Mol Cell"},{"key":"6767_CR10","doi-asserted-by":"publisher","unstructured":"Arndt AK, Schafer S, Drenckhahn JD, Sabeh MK, Plovie ER, Caliebe A, Klopocki E, Musso G, Werdich AA, Kalwa H, Heinig M, Padera RF, Wassilew K, Bluhm J, Harnack C, Martitz J, Barton PJ, Greutmann M, Berger F, Hubner N, \u2026 Klaassen S (2013) Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. American journal of human genetics, 93(1), 67\u201377. https:\/\/doi.org\/10.1016\/j.ajhg.2013.05.015","DOI":"10.1016\/j.ajhg.2013.05.015"},{"issue":"1","key":"6767_CR11","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/j.1365-2141.2011.08918.x","volume":"156","author":"FP Duhoux","year":"2012","unstructured":"Duhoux FP, Ameye G, Montano-Almendras CP, Bahloula K, Mozziconacci MJ, Laibe S, Wlodarska I, Michaux L, Talmant P, Richebourg S, Lippert E, Speleman F, Herens C, Struski S, Raynaud S, Auger N, Nadal N, Rack K, Mugneret F, Tigaud I, Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO) (2012) PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies. Br J Haematol 156(1):76\u201388. https:\/\/doi.org\/10.1111\/j.1365-2141.2011.08918.x","journal-title":"Br J Haematol"},{"issue":"3","key":"6767_CR12","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1111\/bjh.12855","volume":"166","author":"R Masetti","year":"2014","unstructured":"Masetti R, Togni M, Astolfi A, Pigazzi M, Indio V, Rivalta B, Manara E, Rutella S, Basso G, Pession A, Locatelli F (2014) Whole transcriptome sequencing of a paediatric case of de novo acute myeloid leukaemia with del(5q) reveals RUNX1-USP42 and PRDM16-SKI fusion transcripts. Br J Haematol 166(3):449\u2013452. https:\/\/doi.org\/10.1111\/bjh.12855","journal-title":"Br J Haematol"},{"issue":"3","key":"6767_CR13","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/gcc.20241","volume":"44","author":"I Sakai","year":"2005","unstructured":"Sakai I, Tamura T, Narumi H, Uchida N, Yakushijin Y, Hato T, Fujita S, Yasukawa M (2005) Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22). Genes Chromosomes Cancer 44(3):265\u2013270. https:\/\/doi.org\/10.1002\/gcc.20241","journal-title":"Genes Chromosomes Cancer"},{"issue":"6","key":"6767_CR14","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1038\/sj.leu.2404210","volume":"20","author":"MJ Stevens-Kroef","year":"2006","unstructured":"Stevens-Kroef MJ, Schoenmakers EF, van Kraaij M, Huys E, Vermeulen S, van der Reijden B, van Kessel AG (2006) Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case of t(1;21)(p36;q22)-positive therapy-related AML. Leukemia 20(6):1187\u20131189. https:\/\/doi.org\/10.1038\/sj.leu.2404210","journal-title":"Leukemia"},{"issue":"1","key":"6767_CR15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/16078454.2022.2066306","volume":"27","author":"X Xiang","year":"2022","unstructured":"Xiang X, Lu Q, Xu X, Cai P, Chen S, Pan J, Zeng Z (2022) Prognostic impact of PRDM16 expression in acute myeloid leukemia with normal cytogenetics. Hematology (Amsterdam, Netherlands) 27(1):499\u2013505. https:\/\/doi.org\/10.1080\/16078454.2022.2066306","journal-title":"Hematology (Amsterdam, Netherlands)"},{"issue":"1","key":"6767_CR16","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1080\/10428194.2020.1817436","volume":"62","author":"FT Dao","year":"2021","unstructured":"Dao FT, Chen WM, Long LY, Li LD, Yang L, Wang J, Liu YR, Jiang H, Zhang XH, Jiang Q, Qin YZ (2021) High PRDM16 expression predicts poor outcomes in adult acute myeloid leukemia patients with intermediate cytogenetic risk: a comprehensive cohort study from a single Chinese center. Leuk Lymphoma 62(1):185\u2013193. https:\/\/doi.org\/10.1080\/10428194.2020.1817436","journal-title":"Leuk Lymphoma"},{"issue":"11","key":"6767_CR17","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1002\/gcc.22483","volume":"56","author":"G Yamato","year":"2017","unstructured":"Yamato G, Yamaguchi H, Handa H, Shiba N, Kawamura M, Wakita S, Inokuchi K, Hara Y, Ohki K, Okubo J, Park MJ, Sotomatsu M, Arakawa H, Hayashi Y (2017) Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia. Genes Chromosomes Cancer 56(11):800\u2013809. https:\/\/doi.org\/10.1002\/gcc.22483","journal-title":"Genes Chromosomes Cancer"},{"issue":"5","key":"6767_CR18","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/leu.2015.5","volume":"29","author":"A Jo","year":"2015","unstructured":"Jo A, Mitani S, Shiba N, Hayashi Y, Hara Y, Takahashi H, Tsukimoto I, Tawa A, Horibe K, Tomizawa D, Taga T, Adachi S, Yoshida T, Ichikawa H (2015) High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML. Leukemia 29(5):1076\u20131083. https:\/\/doi.org\/10.1038\/leu.2015.5","journal-title":"Leukemia"},{"issue":"9","key":"6767_CR19","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1182\/blood-2002-12-3944","volume":"102","author":"I Nishikata","year":"2003","unstructured":"Nishikata I, Sasaki H, Iga M, Tateno Y, Imayoshi S, Asou N, Nakamura T, Morishita K (2003) A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood 102(9):3323\u20133332. https:\/\/doi.org\/10.1182\/blood-2002-12-3944","journal-title":"Blood"},{"issue":"7","key":"6767_CR20","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1182\/blood.2018888255","volume":"134","author":"T Hu","year":"2019","unstructured":"Hu T, Morita K, Hill MC, Jiang Y, Kitano A, Saito Y, Wang F, Mao X, Hoegenauer KA, Morishita K, Martin JF, Futreal PA, Takahashi K, Nakada D (2019) PRDM16s transforms megakaryocyte-erythroid progenitors into myeloid leukemia-initiating cells. Blood 134(7):614\u2013625. https:\/\/doi.org\/10.1182\/blood.2018888255","journal-title":"Blood"},{"issue":"12","key":"6767_CR21","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1172\/JCI32390","volume":"117","author":"DC Shing","year":"2007","unstructured":"Shing DC, Trubia M, Marchesi F, Radaelli E, Belloni E, Tapinassi C, Scanziani E, Mecucci C, Crescenzi B, Lahortiga I, Odero MD, Zardo G, Gruszka A, Minucci S, Di Fiore PP, Pelicci PG (2007) Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice. J Clin Invest 117(12):3696\u20133707. https:\/\/doi.org\/10.1172\/JCI32390","journal-title":"J Clin Invest"},{"issue":"8","key":"6767_CR22","doi-asserted-by":"publisher","first-page":"3250","DOI":"10.1172\/JCI99862","volume":"128","author":"DJ Corrigan","year":"2018","unstructured":"Corrigan DJ, Luchsinger LL, Justino de Almeida M, Williams LJ, Strikoudis A, Snoeck HW (2018) PRDM16 isoforms differentially regulate normal and leukemic hematopoiesis and inflammatory gene signature. J Clin Investig 128(8):3250\u20133264. https:\/\/doi.org\/10.1172\/JCI99862","journal-title":"J Clin Investig"},{"issue":"4","key":"6767_CR23","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1111\/bjh.13869","volume":"172","author":"N Shiba","year":"2016","unstructured":"Shiba N, Ohki K, Kobayashi T, Hara Y, Yamato G, Tanoshima R, Ichikawa H, Tomizawa D, Park MJ, Shimada A, Sotomatsu M, Arakawa H, Horibe K, Adachi S, Taga T, Tawa A, Hayashi Y (2016) High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia\/Lymphoma Study Group AML-05 trial. Br J Haematol 172(4):581\u2013591. https:\/\/doi.org\/10.1111\/bjh.13869","journal-title":"Br J Haematol"},{"issue":"11","key":"6767_CR24","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.exphem.2003.08.003","volume":"31","author":"B van Waalwijk","year":"2003","unstructured":"van Waalwijk B, van Doorn-Khosrovani S, Erpelinck C, L\u00f6wenberg B, Delwel R (2003) Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia. Exp Hematol 31(11):1066\u20131072. https:\/\/doi.org\/10.1016\/j.exphem.2003.08.003","journal-title":"Exp Hematol"},{"issue":"11","key":"6767_CR25","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1182\/blood-2013-10-534735","volume":"124","author":"H Yu","year":"2014","unstructured":"Yu H, Neale G, Zhang H, Lee HM, Ma Z, Zhou S, Forget BG, Sorrentino BP (2014) Downregulation of Prdm16 mRNA is a specific antileukemic mechanism during HOXB4-mediated HSC expansion in vivo. Blood 124(11):1737\u20131747. https:\/\/doi.org\/10.1182\/blood-2013-10-534735","journal-title":"Blood"},{"issue":"3","key":"6767_CR26","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1056\/NEJMoa041974","volume":"352","author":"B Falini","year":"2005","unstructured":"Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci P-G, Martelli MF (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352(3):254\u2013266. https:\/\/doi.org\/10.1056\/NEJMoa041974","journal-title":"N Engl J Med"},{"issue":"1","key":"6767_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00858-y","volume":"13","author":"JA Georgi","year":"2023","unstructured":"Georgi JA, Stasik S, Eckardt JN, Zukunft S, Hartwig M, R\u00f6llig C, Middeke JM, Oelschl\u00e4gel U, Krug U, Sauer T, Scholl S, Hochhaus A, Br\u00fcmmendorf TH, Naumann R, Steffen B, Einsele H, Schaich M, Burchert A, Neubauer A, Sch\u00e4fer-Eckart K, Schliemann C, Krause SW, H\u00e4nel M, Noppeney R, Kaiser U, Baldus CD, Kaufmann M, M\u00fcller-Tidow C, Platzbecker U, Berdel WE, Serve H, Ehninger G, Bornh\u00e4user M, Schetelig J, Kroschinsky F, Thiede C (2023) UBTF tandem duplications are rare but recurrent alterations in adult AML and associated with younger age, myelodysplasia, and inferior outcome. Blood Cancer J 13(1):88. https:\/\/doi.org\/10.1038\/s41408-023-00858-y","journal-title":"Blood Cancer J"},{"issue":"11","key":"6767_CR28","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1182\/blood.2019003339","volume":"135","author":"MF Bezerra","year":"2020","unstructured":"Bezerra MF, Lima AS, Piqu\u00e9-Borr\u00e0s MR, Silveira DR, Coelho-Silva JL, Pereira-Martins DA, Weinh\u00e4user I, Franca-Neto PL, Quek L, Corby A, Oliveira MM, Lima MM, de Assis RA, de Melo Campos P, Duarte BK, Bendit I, Rocha V, Rego EM, Traina F, Saad ST, Lucena-Araujo AR (2020) Co-occurrence of DNMT3A, NPM1, FLT3 mutations identifies a subset of acute myeloid leukemia with adverse prognosis. Blood 135(11):870\u2013875. https:\/\/doi.org\/10.1182\/blood.2019003339","journal-title":"Blood"},{"issue":"4","key":"6767_CR29","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1016\/j.clnu.2020.10.016","volume":"40","author":"L Liu","year":"2021","unstructured":"Liu L, Chen Y, Chen J, Lu M, Guo R, Han J, Zhang Y, Pei X, Ping Z (2021) The relationship between PRDM16 promoter methylation in abdominal subcutaneous and omental adipose tissue and obesity. Clinical nutrition (Edinburgh, Scotland) 40(4):2278\u20132284. https:\/\/doi.org\/10.1016\/j.clnu.2020.10.016","journal-title":"Clinical nutrition (Edinburgh, Scotland)"},{"key":"6767_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111634","volume":"127","author":"Y Wang","year":"2025","unstructured":"Wang Y, Zheng S, Gao H, Wang Y, Chen Y, Han A (2025) DNA methylation-induced suppression of PRDM16 in colorectal cancer metastasis through the PPAR\u03b3\/EMT pathway. Cell Signal 127:111634. https:\/\/doi.org\/10.1016\/j.cellsig.2025.111634","journal-title":"Cell Signal"},{"issue":"4","key":"6767_CR31","doi-asserted-by":"publisher","first-page":"5007","DOI":"10.18632\/oncotarget.6652","volume":"7","author":"Q Lei","year":"2016","unstructured":"Lei Q, Liu X, Fu H, Sun Y, Wang L, Xu G, Wang W, Yu Z, Liu C, Li P, Feng J, Li G, Wu M (2016) Mir-101 reverses hypomethylation of the PRDM16 promoter to disrupt mitochondrial function in astrocytoma cells. Oncotarget 7(4):5007\u20135022. https:\/\/doi.org\/10.18632\/oncotarget.6652","journal-title":"Oncotarget"},{"issue":"6","key":"6767_CR32","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ccr.2010.11.015","volume":"18","author":"ME Figueroa","year":"2010","unstructured":"Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, L\u00f6wenberg B, Licht JD, Godley LA, Delwel R, Valk PJM, Thompson CB, Levine RL, Melnick A (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18(6):553\u2013567. https:\/\/doi.org\/10.1016\/j.ccr.2010.11.015","journal-title":"Cancer Cell"},{"issue":"1","key":"6767_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26093-2","volume":"12","author":"M Tulstrup","year":"2021","unstructured":"Tulstrup M, Soerensen M, Hansen JW, Gillberg L, Needhamsen M, Kaastrup K, Helin K, Christensen K, Weischenfeldt J, Gr\u00f8nb\u00e6k K (2021) TET2 mutations are associated with hypermethylation at key regulatory enhancers in normal and malignant hematopoiesis. Nat Commun 12(1):6061. https:\/\/doi.org\/10.1038\/s41467-021-26093-2","journal-title":"Nat Commun"},{"issue":"6","key":"6767_CR34","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1182\/blood-2017-01-762393","volume":"131","author":"A Kon","year":"2018","unstructured":"Kon A, Yamazaki S, Nannya Y, Kataoka K, Ota Y, Nakagawa MM, Yoshida K, Shiozawa Y, Morita M, Yoshizato T, Sanada M, Nakayama M, Koseki H, Nakauchi H, Ogawa S (2018) Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice. Blood 131(6):621\u2013635. https:\/\/doi.org\/10.1182\/blood-2017-01-762393","journal-title":"Blood"},{"issue":"6","key":"6767_CR35","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1182\/blood-2018-04-845602","volume":"132","author":"MF Smeets","year":"2018","unstructured":"Smeets MF, Tan SY, Xu JJ, Anande G, Unnikrishnan A, Chalk AM, Taylor SR, Pimanda JE, Wall M, Purton LE, Walkley CR (2018) Srsf2P95H initiates myeloid bias and myelodysplastic\/myeloproliferative syndrome from hemopoietic stem cells. Blood 132(6):608\u2013621. https:\/\/doi.org\/10.1182\/blood-2018-04-845602","journal-title":"Blood"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06767-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-06767-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06767-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:03:44Z","timestamp":1771398224000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-06767-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["6767"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-06767-x","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"assertion":[{"value":"8 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All samples were collected with written informed consent and after approval by the local ethics committee of the Medical Faculty Carl Gustav Carus Dresden, Germany. The study protocols were designed and applied in accordance with the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical Trial Number"}},{"value":"All patients were treated with intensive regimens in the following clinical trials: AML96 (NCT00180115), AML2003 (NCT00180102), AML60\u2009+\u2009(NCT00180167), and SORAML (NCT00893373) or were enrolled in the German Study Alliance Leukemia (SAL)\u2019s AML registry (NCT03188874).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical Trial Registration"}},{"value":"I confirm that no material requiring permission to reproduce from other sources has been included in the paper.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Permission to reproduce material from other sources"}},{"value":"CT is CEO and co-owner of AgenDix GmbH, a company performing molecular diagnostics. The remaining authors declare no conflict of interest.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"49"}}