{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:30:33Z","timestamp":1747193433108,"version":"3.40.5"},"reference-count":20,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Case Rep Oncol"],"abstract":"Hematological malignancies, including chronic myeloid leukemia (CML), exhibit <i>ASXL1<\/i> mutations; however, the function and molecular mechanism of these mutations remain unclear. <i>ASXL1<\/i> was originally identified as tumor suppressor gene, in which loss of function causes myelodysplastic syndrome (MDS). <i>ASXL1<\/i> mutations are common and associated with disease progression in myeloid malignancies including MDS, acute myeloid leukemia, and similarly in CML. In MDS, <i>ASXL1<\/i> mutations have been associated with poor prognosis; however, the impact of <i>ASXL1<\/i> mutations in CML has not been well described. A 31-year-old male was diagnosed as CML-chronic phase (CP). Laboratory findings showed a white blood cell count of 187,200\/\u00b5L, with asymptomatic splenomegaly. Blast count was 5.0% in peripheral blood and 7.3% in bone marrow. There was no additional chromosomal abnormality except for t(9;22)(q34;q11.2) by chromosomal analysis. At onset, the Sokal score was 1.4, indicating high risk. The patient received tyrosine kinase inhibitor (TKI) therapy, comprising nilotinib \u223c600 mg\/day, bosutinib \u223c600 mg\/day, ponatinib \u223c45 mg\/day, and dasatinib \u223c100 mg\/day. Nevertheless, after 1.5 years of continuous TKI therapy, the best outcome was a hematological response. Although additional chromosomal aberrations and <i>ABL1<\/i> kinase mutations were analyzed repeatedly before and during TKI therapy, known genetic abnormalities were not detected. Thereafter, the patient underwent bone marrow transplantation from an HLA 7\/8 matched unrelated donor (HLA-Cw 1 locus mismatch, graft-versus-host direction). The patient achieved neutrophil engraftment, 18 days after transplantation, leading to complete remission with an undetectable level of <i>BCR-ABL1<\/i> mRNA. The patient, however, died from graft-versus-host disease and thrombotic microangiopathy after 121 days. Gene sequence analysis of his CML cell before stem cell transplantation revealed <i>ASXL1<\/i> mutations. Physiologically, <i>ASXL1<\/i> contributes to epigenetic regulation. In the CML-CP patient in this case report, <i>ASXL1<\/i> mutation conferred resistance to TKI through obscure resistance mechanisms. Even though a molecular mechanism for TKI resistance in <i>ASXL1<\/i> mutation in CML has remained obscure, epigenetic modulation is a plausible mode of CML disease progression. The clinical impact including prognosis of <i>ASXL1<\/i> for CML is underscored. And the treatment strategy of CML with <i>ASXL1<\/i> mutation has not been established. A discussion of this case was expected to facilitate treatment options. <\/jats:p>","DOI":"10.1159\/000506452","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T21:00:35Z","timestamp":1587589235000},"page":"449-455","source":"Crossref","is-referenced-by-count":4,"title":["A Case of Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia, Chronic Phase with ASXL1 Mutation"],"prefix":"10.1159","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5332-1316","authenticated-orcid":false,"given":"Osamu","family":"Imataki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhito","family":"Nanya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimihiro","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seishi","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norimitsu","family":"Kadowaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25342"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1567"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.04.007"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2012.1.56"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07697.x"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.298"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2017.36"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409405"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408617"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3733"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12515"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.032"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12217"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013343"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-5-12"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.20"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2015.05.009"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.65"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-708560"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1053\/shem.2002.36921"}],"container-title":["Case Reports in Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/506452","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/506452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:50:52Z","timestamp":1745423452000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000506452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,22]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,5,5]]}},"URL":"https:\/\/doi.org\/10.1159\/000506452","archive":["Portico"],"relation":{},"ISSN":["1662-6575"],"issn-type":[{"type":"electronic","value":"1662-6575"}],"subject":[],"published":{"date-parts":[[2020,4,22]]}}}