{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T17:20:04Z","timestamp":1765041604762,"version":"3.44.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["JP23K24298"],"award-info":[{"award-number":["JP23K24298"]}]},{"DOI":"10.13039\/100021092","name":"University of Yamanashi","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100021092","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>In Philadelphia chromosome-positive (Ph +) leukemia, substitution of threonine at the 315 position of BCR::ABL1 with isoleucine (T315I) induces severe resistance to tyrosine kinase inhibitors (TKIs). Of clinical importance, the substitution of the baseline T315I mutation by methionine (I315M) was reported in a Ph +\u2009leukemia patient treated with ponatinib. The resultant T315M mutation induces severe TKI-resistance in a murine Ba\/F3 model. Asciminib, an allosteric inhibitor of BCR::ABL1, is reportedly active in ponatinib-resistant patients with the T315I mutation. Although asciminib alone is not active in a murine Ba\/F3 model with the T315M mutation, asciminib and ponatinib show synergistic activities. In the present study, we introduced the T315M mutation into the intrinsic <jats:italic>BCR::ABL1<\/jats:italic> gene of two Ph +\u2009myeloid and one Ph +\u2009lymphoid leukemia cell lines using the CRISPR\/Cas9 system to directly verify the utility of the combined asciminib and ponatinib in human models. All three T315M-acquired sublines were more resistant to TKIs including ponatinib than T315I-acquired sublines. Notably, asciminib exhibited a stronger synergistic effect with reduced doses of ponatinib in the T315M-acquired sublines of two myeloid cell lines, but not in the lymphoid cell line. This indicates that the combination of ponatinib and asciminib may have a clinical utility in human Ph +\u2009myeloid leukemia.<\/jats:p>","DOI":"10.1007\/s12185-025-03981-7","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T06:46:03Z","timestamp":1744267563000},"page":"206-216","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic effect of asciminib with reduced doses of ponatinib in human Ph +\u2009myeloid leukemia with the T315M mutation"],"prefix":"10.1007","volume":"122","author":[{"given":"Thao","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Harama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minori","family":"Tamai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Kagami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiaki","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Kasai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koshi","family":"Akahane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumiko","family":"Goi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Inukai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"3981_CR1","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/S0140-6736(13)62120-0","volume":"385","author":"JF Apperley","year":"2015","unstructured":"Apperley JF. Chronic myeloid leukemia. Lancet. 2015;385:1447\u201359.","journal-title":"Lancet"},{"key":"3981_CR2","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1182\/blood-2018-08-832105","volume":"133","author":"F Ravandi","year":"2019","unstructured":"Ravandi F. How I treat Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2019;133:130\u20136.","journal-title":"Blood"},{"key":"3981_CR3","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nrc3317","volume":"12","author":"T O\u2019Hare","year":"2012","unstructured":"O\u2019Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of targeted therapy in chronic myeloid leukemia. Nat Rev Cancer. 2012;12:513\u201326.","journal-title":"Nat Rev Cancer"},{"key":"3981_CR4","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1126\/science.1062538","volume":"293","author":"ME Gorre","year":"2001","unstructured":"Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876\u201380.","journal-title":"Science"},{"key":"3981_CR5","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ccr.2009.09.028","volume":"16","author":"T O\u2019Hare","year":"2009","unstructured":"O\u2019Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16:401\u201312.","journal-title":"Cancer Cell"},{"key":"3981_CR6","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1056\/NEJMoa1205127","volume":"367","author":"JE Cortes","year":"2012","unstructured":"Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, et al. Ponatinib in refractory Philadelphia chromosome\u2013positive leukemias. N Engl J Med. 2012;367:2075\u201388.","journal-title":"N Engl J Med"},{"key":"3981_CR7","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.ccr.2014.07.006","volume":"26","author":"MS Zabriskie","year":"2014","unstructured":"Zabriskie MS, Eide CA, Tantravahi SK, Vellore NA, Estrada J, Nicolini FE, et al. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell. 2014;26:428\u201342.","journal-title":"Cancer Cell"},{"key":"3981_CR8","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1158\/0008-5472.CAN-10-3224","volume":"71","author":"CA Eide","year":"2011","unstructured":"Eide CA, Adrian LT, Tyner JW, Partlin MM, Anderson DJ, Wise SC, et al. The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile. Cancer Res. 2011;71:3189\u201395.","journal-title":"Cancer Res"},{"key":"3981_CR9","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1182\/blood-2012-05-431379","volume":"121","author":"JS Khorashad","year":"2013","unstructured":"Khorashad JS, Kelley TW, Szankasi P, Mason CC, Soverini S, Adrian LT, et al. BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: frequency and clonal relationships. Blood. 2013;121:489\u201398.","journal-title":"Blood"},{"key":"3981_CR10","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1182\/blood-2015-08-660977","volume":"127","author":"MW Deininger","year":"2016","unstructured":"Deininger MW, Hodgson JG, Shah NP, Cortes JE, Kim DW, Nicolini FE, et al. Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients. Blood. 2016;127:703\u201312.","journal-title":"Blood"},{"key":"3981_CR11","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nature21702","volume":"543","author":"AA Wylie","year":"2017","unstructured":"Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017;543:733\u20137.","journal-title":"Nature"},{"key":"3981_CR12","doi-asserted-by":"publisher","first-page":"3474","DOI":"10.1182\/blood.2021014689","volume":"139","author":"DT Yeung","year":"2022","unstructured":"Yeung DT, Shanmuganathan N, Hughes TP. Asciminib: a new therapeutic option in chronic-phase CML with treatment failure. Blood. 2022;139:3474\u20139.","journal-title":"Blood"},{"key":"3981_CR13","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.ccell.2019.08.004","volume":"36","author":"CA Eide","year":"2019","unstructured":"Eide CA, Zabriskie MS, Stevens SLS, Antelope O, Vellore NA, Than H, et al. Combining the allosteric inhibitor asciminib with ponatinib suppresses emergence of and restores efficacy against highly resistant BCR-ABL1 mutants. Cancer Cell. 2019;36:431\u201343.","journal-title":"Cancer Cell"},{"key":"3981_CR14","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1056\/NEJMoa1902328","volume":"381","author":"TP Hughes","year":"2019","unstructured":"Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ, et al. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N Engl J Med. 2019;381:2315\u201326.","journal-title":"N Engl J Med"},{"key":"3981_CR15","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1007\/s00277-022-04932-6","volume":"101","author":"A Luna","year":"2022","unstructured":"Luna A, P\u00e9rez-Lamas L, Boque C, Giraldo P, Xicoy B, Nu\u00f1o CR, et al. Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia. Ann Hematol. 2022;101:2263\u201370.","journal-title":"Ann Hematol"},{"key":"3981_CR16","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1038\/s41375-024-02278-8","volume":"38","author":"JE Cortes","year":"2024","unstructured":"Cortes JE, Sasaki K, Kim DW, Hughes TP, Etienne G, Mauro MJ, et al. Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after 1 prior tyrosine kinase inhibitor: 2-year follow-up results. Leukemia. 2024;38:1522\u201333.","journal-title":"Leukemia"},{"key":"3981_CR17","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ccr.2008.04.018","volume":"13","author":"MJ Bueno","year":"2008","unstructured":"Bueno MJ, de Castro IP, de Cedr\u00f3n MMG, Santos J, Calin GA, Cigudosa JC, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13:496\u2013506.","journal-title":"Cancer Cell"},{"key":"3981_CR18","doi-asserted-by":"publisher","first-page":"3834","DOI":"10.1158\/1535-7163.MCT-08-0482","volume":"7","author":"TS Lee","year":"2008","unstructured":"Lee TS, Ma W, Zhang X, Giles F, Cortes J, Kantarjian H, et al. BCR-ABL alternative splicing as a common mechanism for imatinib resistance: evidence from molecular dynamics simulations. Mol Cancer Ther. 2008;7:3834\u201341.","journal-title":"Mol Cancer Ther"},{"key":"3981_CR19","doi-asserted-by":"publisher","first-page":"9966","DOI":"10.1038\/s41598-018-27767-6","volume":"8","author":"M Tamai","year":"2018","unstructured":"Tamai M, Inukai T, Kojika S, Abe M, Kagami K, Harama D, et al. T315I mutation of BCR-ABL1 into human Philadelphia chromosome-positive leukemia cell lines by homologous recombination using the CRISPR\/Cas9 system. Sci Rep. 2018;8:9966.","journal-title":"Sci Rep"},{"key":"3981_CR20","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1007\/s12185-022-03369-x","volume":"116","author":"TT Nguyen","year":"2022","unstructured":"Nguyen TT, Tamai M, Harama D, Kagami K, Kasai S, Watanabe A, et al. Introduction of the T315I gatekeeper mutation of BCR\/ABL1 into a Philadelphia chromosome-positive lymphoid leukemia cell line using the CRISPR\/Cas9 system. Int J Hematol. 2022;116:534\u201343.","journal-title":"Int J Hematol"},{"key":"3981_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1749-0774.2005.tb00054.x","volume":"18","author":"PNT Van","year":"2005","unstructured":"Van PNT, Xinh PT, Kano Y, Tokunaga K, Sato Y. Establishment and characterization of A novel Philadelphia-chromosome positive chronic myeloid leukemia cell line, TCC-S, expressing P210 and P190 BCR\/ABL transcripts but missing normal ABL gene. Hum Cell. 2005;18:25\u201333.","journal-title":"Hum Cell"},{"key":"3981_CR22","doi-asserted-by":"publisher","first-page":"3658","DOI":"10.1182\/blood-2002-06-1770","volume":"101","author":"K Uno","year":"2003","unstructured":"Uno K, Inukai T, Kayagaki N, Goi K, Sato H, Nemoto A, et al. TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome\u2013positive leukemia cells. Blood. 2003;101:3658\u201367.","journal-title":"Blood"},{"key":"3981_CR23","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nbt.3190","volume":"33","author":"T Maruyama","year":"2015","unstructured":"Maruyama T, Dougan SK, Truttmann MC, Bilate AM, Ingram JR, Ploegh HL. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nature Biotechnol. 2015;33:538.","journal-title":"Nature Biotechnol"},{"key":"3981_CR24","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.gpb.2022.01.004","volume":"20","author":"S Zheng","year":"2022","unstructured":"Zheng S, Wang W, Aldahdooh J, Malyutina A, Shadbahr T, Tanoli Z, et al. SynergyFinder Plus: Toward better interpretation and annotation of drug combination screening datasets. Genomics Proteomics Bioinformatics. 2022;20:587\u201396.","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"3981_CR25","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.csbj.2015.09.001","volume":"13","author":"B Yadav","year":"2015","unstructured":"Yadav B, Wennerberg K, Aittokallio T, Tang J. Searching for drug synergy in complex dose-response landscapes using an interaction potency model. Comput Struct Biotechnol J. 2015;13:504\u201313.","journal-title":"Comput Struct Biotechnol J"},{"key":"3981_CR26","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1126\/science.1099480","volume":"305","author":"NP Shah","year":"2004","unstructured":"Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004;305:399\u2013401.","journal-title":"Science"},{"key":"3981_CR27","doi-asserted-by":"publisher","first-page":"879","DOI":"10.2165\/00003088-200544090-00001","volume":"44","author":"B Peng","year":"2005","unstructured":"Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44:879\u201394.","journal-title":"Clin Pharmacokinet"},{"key":"3981_CR28","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1002\/jcph.1312","volume":"58","author":"X Tian","year":"2018","unstructured":"Tian X, Zhang H, Heimbach T, He H, Buchbinder A, Aghoghovbia M, et al. Clinical pharmacokinetic and pharmacodynamic overview of nilotinib, a selective tyrosine kinase inhibitor. J Clin Pharmacol. 2018;58:1533\u201340.","journal-title":"J Clin Pharmacol"},{"key":"3981_CR29","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s00228-015-1968-y","volume":"72","author":"Y Ishida","year":"2016","unstructured":"Ishida Y, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Ogawa K, et al. Pharmacokinetics and pharmacodynamics of dasatinib in the chronic phase of newly diagnosed chronic myeloid leukemia. Eur J Clin Pharmacol. 2016;72:185\u201393.","journal-title":"Eur J Clin Pharmacol"},{"key":"3981_CR30","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/jcph.1990","volume":"62","author":"MJ Hanley","year":"2022","unstructured":"Hanley MJ, Diderichsen PM, Narasimhan N, Srivastava S, Gupta N, Venkatakrishnan K. Population pharmacokinetics of ponatinib in healthy adult volunteers and patients with hematologic malignancies and model-informed dose selection for pediatric development. J Clinl Pharmacol. 2022;62:555\u201367.","journal-title":"J Clinl Pharmacol"},{"key":"3981_CR31","doi-asserted-by":"publisher","first-page":"4210","DOI":"10.1200\/JCO.2015.62.4718","volume":"33","author":"JJ Moslehi","year":"2015","unstructured":"Moslehi JJ, Deininger M. Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol. 2015;33:4210\u20138.","journal-title":"J Clin Oncol"},{"key":"3981_CR32","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1182\/blood-2016-09-739086","volume":"132","author":"JE Cortes","year":"2018","unstructured":"Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393\u2013404.","journal-title":"Blood"},{"key":"3981_CR33","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1038\/s41375-024-02248-0","volume":"38","author":"N Curik","year":"2024","unstructured":"Curik N, Laznicka A, Polivkova V, Krizkova J, Pokorna E, Semerak P, et al. Combination therapies with ponatinib and asciminib in a preclinical model of chronic myeloid leukemia blast crisis with compound mutations. Leukemia. 2024;38:1415\u20138.","journal-title":"Leukemia"},{"key":"3981_CR34","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1016\/j.ccell.2024.08.004","volume":"42","author":"CA Eide","year":"2024","unstructured":"Eide CA, Brewer D, Xie T, Schultz AR, Savage SL, Muratcioglu S, et al. Overcoming clinical BCR-ABL1 compound mutant resistance with combined ponatinib and asciminib therapy. Cancer Cell. 2024;42:1486\u20138.","journal-title":"Cancer Cell"},{"key":"3981_CR35","doi-asserted-by":"publisher","first-page":"261","DOI":"10.14740\/jmc4287","volume":"15","author":"A Amin Muhammad","year":"2024","unstructured":"Amin Muhammad A, Mir Ghazi E, Ali A, Tam E, Woan K, Chaudhary P, et al. Combination therapy with asciminib and ponatinib as a bridge to brexucabtagene autoleucel and maintenance in a patient with relapsed refractory Philadelphia positive B-cell acute lymphoblastic leukemia. J Med Cases. 2024;15:261\u20136.","journal-title":"J Med Cases"},{"key":"3981_CR36","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/nrc2900","volume":"10","author":"W Kolch","year":"2010","unstructured":"Kolch W, Pitt A. Functional proteomics to dissect tyrosine kinase signaling pathways in cancer. Nat Rev Cancer. 2010;10:618\u201329.","journal-title":"Nat Rev Cancer"},{"key":"3981_CR37","doi-asserted-by":"publisher","first-page":"7414","DOI":"10.1073\/pnas.0900653106","volume":"106","author":"B Brehme","year":"2009","unstructured":"Brehme B, Hantschel O, Colinge J, Kaupe I, Planyavsky M, K\u00f6cher T, et al. Charting the molecular network of the drug target Bcr-Abl. Proc Natl Acad Sci USA. 2009;106:7414\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3981_CR38","doi-asserted-by":"publisher","first-page":"4888","DOI":"10.1182\/blood-2005-08-3399","volume":"107","author":"VL Goss","year":"2006","unstructured":"Goss VL, Lee KA, Moritz A, Nardone J, Spek EJ, MacNeill J, et al. A common phosphotyrosine signature for the Bcr-Abl kinase. Blood. 2006;107:4888\u201397.","journal-title":"Blood"},{"key":"3981_CR39","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S0092-8674(85)80053-2","volume":"41","author":"R Palacios","year":"1985","unstructured":"Palacios R, Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985;41:727\u201334.","journal-title":"Cell"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-03981-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-025-03981-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-03981-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T11:26:36Z","timestamp":1757157996000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-025-03981-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["3981"],"URL":"https:\/\/doi.org\/10.1007\/s12185-025-03981-7","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"type":"print","value":"0925-5710"},{"type":"electronic","value":"1865-3774"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"27 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}