{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T09:21:52Z","timestamp":1753521712308,"version":"3.37.3"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>BCR-ABL1 kinase inhibitors have improved the prognosis of Philadelphia-chromosome-positive (Ph+)-acute lymphoblastic leukemia (ALL). Ph-like (or BCR-ABL1-like) ALL does not express BCR-ABL1 but commonly harbors other genomic alterations of signaling molecules that may be amenable to therapy. Here, we report a case with a NUP214-ABL1 fusion detected at relapse by multiplexed, targeted RNA sequencing. It had escaped conventional molecular work-up at diagnosis, including cytogenetic analysis and fluorescence in situ hybridization for ABL1 rearrangements. The patient had responded poorly to initial multi-agent chemotherapy and inotuzumab immunotherapy at relapse before the fusion was revealed. The addition of dasatinib targeting NUP214-ABL1 to inotuzumab resulted in complete molecular remission, but recurrence occurred rapidly with dasatinib alone. However, deep molecular remission was recaptured with a combination of blinatumomab and ponatinib, so he could proceed to allotransplantation. This case illustrates that next-generation sequencing approaches designed to discover cryptic gene fusions can benefit patients with Ph-like ALL.<\/jats:p>","DOI":"10.1093\/oncolo\/oyab052","type":"journal-article","created":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T05:00:52Z","timestamp":1641013252000},"page":"82-86","source":"Crossref","is-referenced-by-count":7,"title":["Chemotherapy Resistance in B-ALL with Cryptic <i>NUP214-ABL1<\/i> Is Amenable to Kinase Inhibition and Immunotherapy"],"prefix":"10.1093","volume":"27","author":[{"given":"Valentina","family":"Nardi","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Department of Pathology, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L","family":"McAfee","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Dal Cin","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harrison K","family":"Tsai","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Department of Pathology, Boston Children\u2019s Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip C","family":"Amrein","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela S","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M","family":"Brunner","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupa","family":"Narayan","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Foster","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir T","family":"Fathi","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5201-9403","authenticated-orcid":false,"given":"Hanno","family":"Hock","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Center, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Harvard Stem Cell Institute, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"issue":"14","key":"2022030711014565700_CIT0001","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1182\/blood-2018-10-881961","article-title":"A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403.","volume":"133","author":"Stock","year":"2019","journal-title":"Blood."},{"issue":"20","key":"2022030711014565700_CIT0002","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1200\/JCO.2015.62.4544","article-title":"Dexamethasone and High-Dose Methotrexate improve outcome for children and young adults with high-risk B-Acute Lymphoblastic Leukemia: a report from children\u2019s oncology group study AALL0232.","volume":"34","author":"Larsen","year":"2016","journal-title":"J Clin Oncol."},{"key":"2022030711014565700_CIT0003","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1182\/blood-2019-129018","article-title":"Sequential combination of inotuzumab ozogamicin (ino) with low-intensity chemotherapy (mini-hyper-cvd) with or without blinatumomab is highly effective in patients (pts) with philadelphia chromosome-negative acute lymphoblastic leukemia (all) in first relapse.","volume":"134","author":"Sasaki","year":"2019","journal-title":"Blood"},{"issue":"2","key":"2022030711014565700_CIT0004","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ccr.2012.06.005","article-title":"Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.","volume":"22","author":"Roberts","year":"2012","journal-title":"Cancer Cell."},{"issue":"16","key":"2022030711014565700_CIT0005","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1182\/blood.2019001244","article-title":"Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements.","volume":"134","author":"Tanasi","year":"2019","journal-title":"Blood."},{"issue":"2","key":"2022030711014565700_CIT0006","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S1470-2045(08)70339-5","article-title":"A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.","volume":"10","author":"Den Boer","year":"2009","journal-title":"Lancet Oncol."},{"issue":"5","key":"2022030711014565700_CIT0007","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1056\/NEJMoa0808253","article-title":"Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.","volume":"360","author":"Mullighan","year":"2009","journal-title":"N Engl J Med."},{"issue":"11","key":"2022030711014565700_CIT0008","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1056\/NEJMoa1403088","article-title":"Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.","volume":"371","author":"Roberts","year":"2014","journal-title":"N Engl J Med."},{"issue":"1","key":"2022030711014565700_CIT0009","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1182\/bloodadvances.2019000769","article-title":"Clinical response to larotrectinib in adult Philadelphia chromosome-like ALL with cryptic ETV6-NTRK3 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