{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T08:03:00Z","timestamp":1771401780779,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0111000"],"award-info":[{"award-number":["2019YFA0111000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>KIT<\/jats:italic>\n                    mutations are well-established as poor prognostic markers in core binding factor AML (CBF AML). However, data on\n                    <jats:italic>KIT<\/jats:italic>\n                    mutation in CBF-negative (CBF-neg) AML remains scarce. This retrospective study aimed to characterize the clinical features and outcomes of patients with\n                    <jats:italic>KIT<\/jats:italic>\n                    mutant (\n                    <jats:italic>KIT<\/jats:italic>\n                    mut)\/CBF-neg AML. We conducted a retrospective study in our single center and identified non-M3 de novo AML with KIT mutations by next-generation sequencing (NGS) from January 2018 to June 2024. Core binding factor (CBF) AML or patients with underlying systemic mastocytosis were excluded. The clinical data of\n                    <jats:italic>KIT<\/jats:italic>\n                    mut\/CBF-neg AML was collected and analyzed. 45 patients were enrolled in the cohort, including 3 patients with secondary AML. The median variant allele frequency (VAF) of\n                    <jats:italic>KIT<\/jats:italic>\n                    mutation was 41.2% and the most frequent comuations were\n                    <jats:italic>CEBPA<\/jats:italic>\n                    (27\/45, 60%),\n                    <jats:italic>WT1<\/jats:italic>\n                    (12\/45, 26.7%) and\n                    <jats:italic>NRAS<\/jats:italic>\n                    (11\/45, 24.4%). After a median follow-up of 48 months, the median event-free survival (EFS) and overall survival (OS) of the cohort was 15.3 months and 24.1 months, respectively. Patients with\n                    <jats:italic>KIT<\/jats:italic>\n                    exon 17 mutations tended to harbor an inferior EFS and OS. In conclusion,\n                    <jats:italic>KIT<\/jats:italic>\n                    mutant\/CBF-neg AML was a complex subgroup with dismal prognosis and NIT might bring benefits for those patients.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-06814-7","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T07:43:40Z","timestamp":1768895020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["KIT Mutant\/Core binding factor-negative acute myeloid leukemia might be a complex subgroup with dismal prognosis: a single-center retrospective analysis"],"prefix":"10.1007","volume":"105","author":[{"given":"Rui","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqiang","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"2","key":"6814_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2021.188631","volume":"1876","author":"S Pathania","year":"2021","unstructured":"Pathania S, Pentikainen OT, Singh PK (2021) A holistic view on c-Kit in cancer: structure, signaling, pathophysiology and its inhibitors. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1876(2):188631. https:\/\/doi.org\/10.1016\/j.bbcan.2021.188631","journal-title":"Biochimica et Biophysica Acta (BBA) - Reviews on Cancer"},{"issue":"4","key":"6814_CR2","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1152\/physrev.00046.2011","volume":"92","author":"J Lennartsson","year":"2012","unstructured":"Lennartsson J, Ronnstrand L (2012) Stem cell factor receptor\/c-Kit: from basic science to clinical implications. Physiol Rev 92(4):1619\u20131649. https:\/\/doi.org\/10.1152\/physrev.00046.2011","journal-title":"Physiol Rev"},{"issue":"11","key":"6814_CR3","doi-asserted-by":"publisher","first-page":"9159","DOI":"10.1074\/jbc.M211726200","volume":"278","author":"O Voytyuk","year":"2003","unstructured":"Voytyuk O, Lennartsson J, Mogi A, Caruana G, Courtneidge S, Ashman LK et al (2003) Src family kinases are involved in the differential signaling from two splice forms of c-Kit. J Biol Chem 278(11):9159\u20139166. https:\/\/doi.org\/10.1074\/jbc.M211726200","journal-title":"J Biol Chem"},{"issue":"1","key":"6814_CR4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1182\/blood-2003-07-2554","volume":"104","author":"E Wandzioch","year":"2004","unstructured":"Wandzioch E, Edling CE, Palmer RH, Carlsson L, Hallberg B (2004) Activation of the MAP kinase pathway by c-Kit is PI-3 kinase dependent in hematopoietic progenitor\/stem cell lines. Blood 104(1):51\u201357. https:\/\/doi.org\/10.1182\/blood-2003-07-2554","journal-title":"Blood"},{"issue":"9","key":"6814_CR5","doi-asserted-by":"publisher","first-page":"3688","DOI":"10.1182\/blood.V87.9.3688.bloodjournal8793688","volume":"87","author":"SR Weiler","year":"1996","unstructured":"Weiler SR, Mou S, DeBerry CS, Keller JR, Ruscetti FW, Ferris DK et al (1996) JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor. Blood 87(9):3688\u20133693","journal-title":"Blood"},{"issue":"9","key":"6814_CR6","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1093\/emboj\/21.9.2159","volume":"21","author":"S Zhao","year":"2002","unstructured":"Zhao S, Zoller K, Masuko M, Rojnuckarin P, Yang XO, Parganas E et al (2002) JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive self-renewal of primary multipotential hemopoietic cells. EMBO J 21(9):2159\u20132167. https:\/\/doi.org\/10.1093\/emboj\/21.9.2159","journal-title":"EMBO J"},{"key":"6814_CR7","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.2147\/DDDT.S89114","volume":"10","author":"M Abbaspour Babaei","year":"2016","unstructured":"Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F (2016) Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des Devel Ther 10:2443\u20132459. https:\/\/doi.org\/10.2147\/DDDT.S89114","journal-title":"Drug Des Devel Ther"},{"key":"6814_CR8","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1146\/annurev-pathmechdis-031521-042618","volume":"18","author":"P Valent","year":"2023","unstructured":"Valent P, Akin C, Sperr WR, Horny HP, Arock M, Metcalfe DD et al (2023) New insights into the pathogenesis of mastocytosis: emerging concepts in diagnosis and therapy. Annu Rev Pathol 18:361\u2013386. https:\/\/doi.org\/10.1146\/annurev-pathmechdis-031521-042618","journal-title":"Annu Rev Pathol"},{"issue":"22","key":"6814_CR9","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1056\/NEJMoa1301689","volume":"368","author":"N Research","year":"2013","unstructured":"Cancer Genome Atlas, Research N, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ et al (2013) Genomic and epigenomic landscapes of adult de Novo acute myeloid leukemia. N Engl J Med 368(22):2059\u20132074. https:\/\/doi.org\/10.1056\/NEJMoa1301689","journal-title":"N Engl J Med"},{"issue":"12","key":"6814_CR10","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1056\/NEJMoa1112304","volume":"366","author":"JP Patel","year":"2012","unstructured":"Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J et al (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366(12):1079\u20131089. https:\/\/doi.org\/10.1056\/NEJMoa1112304","journal-title":"N Engl J Med"},{"issue":"1","key":"6814_CR11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1182\/bloodadvances.2019000709","volume":"4","author":"Y Ishikawa","year":"2020","unstructured":"Ishikawa Y, Kawashima N, Atsuta Y, Sugiura I, Sawa M, Dobashi N et al (2020) Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11. Blood Adv 4(1):66\u201375. https:\/\/doi.org\/10.1182\/bloodadvances.2019000709","journal-title":"Blood Adv"},{"issue":"7","key":"6814_CR12","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","volume":"36","author":"JD Khoury","year":"2022","unstructured":"Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF et al (2022) The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic\/dendritic neoplasms. Leukemia 36(7):1703\u20131719. https:\/\/doi.org\/10.1038\/s41375-022-01613-1","journal-title":"Leukemia"},{"issue":"12","key":"6814_CR13","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1182\/blood.2022016867","volume":"140","author":"H Dohner","year":"2022","unstructured":"Dohner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H et al (2022) Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140(12):1345\u20131377. https:\/\/doi.org\/10.1182\/blood.2022016867","journal-title":"Blood"},{"issue":"26","key":"6814_CR14","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1182\/blood.2021013626","volume":"138","author":"M Heuser","year":"2021","unstructured":"Heuser M, Freeman SD, Ossenkoppele GJ, Buccisano F, Hourigan CS, Ngai LL et al (2021) 2021 update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD working party. Blood 138(26):2753\u20132767. https:\/\/doi.org\/10.1182\/blood.2021013626","journal-title":"Blood"},{"issue":"4","key":"6814_CR15","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1182\/bloodadvances.2023012006","volume":"8","author":"Z Zhang","year":"2024","unstructured":"Zhang Z, Yin J, Lian G, Bao X, Hu M, Liu Z et al (2024) A multicenter retrospective comparison between systemic mastocytosis with t(8;21) AML and KIT mutant t(8;21) AML. Blood Adv 8(4):889\u2013894. https:\/\/doi.org\/10.1182\/bloodadvances.2023012006","journal-title":"Blood Adv"},{"key":"6814_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2024.07.009","author":"DH Kim","year":"2024","unstructured":"Kim DH, Jia F, Patel KP, Bose P, Wang SA, Bueso-Ramos C et al (2024) Utility of KIT mutations in myeloid neoplasms without documented systemic mastocytosis to detect hidden mast cells in bone marrow. Clin Lymphoma Myeloma Leuk. https:\/\/doi.org\/10.1016\/j.clml.2024.07.009","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"6814_CR17","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-051022-014433","author":"N Kayagaki","year":"2023","unstructured":"Kayagaki N, Webster JD, Newton K (2023) Control of cell death in health and disease. Annu Rev Pathol. https:\/\/doi.org\/10.1146\/annurev-pathmechdis-051022-014433","journal-title":"Annu Rev Pathol"},{"issue":"1","key":"6814_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.hemonc.2016.08.005","volume":"10","author":"H Ayatollahi","year":"2017","unstructured":"Ayatollahi H, Shajiei A, Sadeghian MH, Sheikhi M, Yazdandoust E, Ghazanfarpour M et al (2017) Prognostic importance of C-KIT mutations in core binding factor acute myeloid leukemia: a systematic review. Hematol Oncol Stem Cell Ther 10(1):1\u20137. https:\/\/doi.org\/10.1016\/j.hemonc.2016.08.005","journal-title":"Hematol Oncol Stem Cell Ther"},{"issue":"9","key":"6814_CR19","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.1182\/blood-2005-09-3640","volume":"107","author":"R Cairoli","year":"2006","unstructured":"Cairoli R, Beghini A, Grillo G, Nadali G, Elice F, Ripamonti CB et al (2006) Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood 107(9):3463\u20133468. https:\/\/doi.org\/10.1182\/blood-2005-09-3640","journal-title":"Blood"},{"issue":"6","key":"6814_CR20","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1038\/s41375-019-0697-0","volume":"34","author":"S Opatz","year":"2020","unstructured":"Opatz S, Bamopoulos SA, Metzeler KH, Herold T, Ksienzyk B, Braundl K et al (2020) The clinical mutatome of core binding factor leukemia. Leukemia 34(6):1553\u20131562. https:\/\/doi.org\/10.1038\/s41375-019-0697-0","journal-title":"Leukemia"},{"issue":"3","key":"6814_CR21","doi-asserted-by":"publisher","first-page":"288","DOI":"10.3343\/alm.2015.35.3.288","volume":"35","author":"SH Park","year":"2015","unstructured":"Park SH, Lee HJ, Kim IS, Kang JE, Lee EY, Kim HJ et al (2015) Incidences and prognostic impact of c-KIT, WT1, CEBPA, and CBL mutations, and mutations associated with epigenetic modification in core binding factor acute myeloid leukemia: a multicenter study in a Korean population. Ann Lab Med 35(3):288\u2013297. https:\/\/doi.org\/10.3343\/alm.2015.35.3.288","journal-title":"Ann Lab Med"},{"issue":"10","key":"6814_CR22","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1007\/s00277-017-3074-y","volume":"96","author":"S Yui","year":"2017","unstructured":"Yui S, Kurosawa S, Yamaguchi H, Kanamori H, Ueki T, Uoshima N et al (2017) D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations. Ann Hematol 96(10):1641\u20131652. https:\/\/doi.org\/10.1007\/s00277-017-3074-y","journal-title":"Ann Hematol"},{"issue":"24","key":"6814_CR23","doi-asserted-by":"publisher","first-page":"21592","DOI":"10.1002\/cam4.6693","volume":"12","author":"Y Zhai","year":"2023","unstructured":"Zhai Y, Wang Q, Ji L, Ren H, Dong Y, Yang F et al (2023) Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world. Cancer Med 12(24):21592\u201321604. https:\/\/doi.org\/10.1002\/cam4.6693","journal-title":"Cancer Med"},{"issue":"Supplement 1","key":"6814_CR24","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1182\/blood-2024-199917","volume":"144","author":"E Kugler","year":"2024","unstructured":"Kugler E, Loghavi S, Ravandi F, DiNardo CD, Daver N, Kadia TM et al (2024) Incidence, characteristics, and outcomes of patients with newly diagnosed, de novoKIT-mutated non-core binding factor acute myeloid leukemia without systemic mastocytosis. Blood 144(Supplement 1):2857\u20132857. https:\/\/doi.org\/10.1182\/blood-2024-199917","journal-title":"Blood"},{"issue":"12","key":"6814_CR25","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1038\/s41375-022-01692-0","volume":"36","author":"NJ Short","year":"2022","unstructured":"Short NJ, Fu C, Berry DA, Walter RB, Freeman SD, Hourigan CS et al (2022) Association of hematologic response and assay sensitivity on the prognostic impact of measurable residual disease in acute myeloid leukemia: a systematic review and meta-analysis. Leukemia 36(12):2817\u20132826. https:\/\/doi.org\/10.1038\/s41375-022-01692-0","journal-title":"Leukemia"},{"issue":"5","key":"6814_CR26","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1182\/bloodadvances.2020003734","volume":"5","author":"M Stahl","year":"2021","unstructured":"Stahl M, Menghrajani K, Derkach A, Chan A, Xiao W, Glass J et al (2021) Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed\/refractory AML. Blood Adv 5(5):1552\u20131564. https:\/\/doi.org\/10.1182\/bloodadvances.2020003734","journal-title":"Blood Adv"},{"issue":"8","key":"6814_CR27","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1002\/ajh.26991","volume":"98","author":"AH Matthews","year":"2023","unstructured":"Matthews AH, Perl AE, Luger SM, Gill SI, Lai C, Porter DL et al (2023) Real-world effectiveness of intensive chemotherapy with 7&3 versus venetoclax and hypomethylating agent in acute myeloid leukemia. Am J Hematol 98(8):1254\u20131264. https:\/\/doi.org\/10.1002\/ajh.26991","journal-title":"Am J Hematol"},{"key":"6814_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bneo.2024.100017","author":"J Othman","year":"2024","unstructured":"Othman J, Lam HPJ, Leong S, Basheer F, Abdallah I, Fleming K et al (2024) Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS. Blood Neoplasia. https:\/\/doi.org\/10.1016\/j.bneo.2024.100017","journal-title":"Blood Neoplasia"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06814-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-06814-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06814-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:03:35Z","timestamp":1771398215000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-06814-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["6814"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-06814-7","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]},"assertion":[{"value":"17 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 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":"This study was performed in line with the principles of the Declaration of Helsinki. The Ethics Committee of First Affiliated Hospital of Soochow University approved this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Informed consent of publication was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42"}}