{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:17:42Z","timestamp":1788967062531,"version":"build-2803163510"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008886","name":"Princess Takamatsu cancer research fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008886","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    BCR\/ABL1 causes dysregulated cell proliferation and is responsible for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). In addition to the deregulatory effects of its kinase activity on cell proliferation, BCR\/ABL1 induces genomic instability by downregulating BRCA1. PARP inhibitors (PARPi) effectively induce cell death in BRCA-defective cells. Therefore, PARPi are expected to inhibit growth of CML and Ph1-ALL cells showing downregulated expression of BRCA1. Here, we show that PARPi effectively induced cell death in BCR\/ABL1 positive cells and suppressed colony forming activity. Prevention of BCR\/ABL1-mediated leukemogenesis by PARP inhibition was tested in two in vivo models: wild-type mice that had undergone hematopoietic cell transplantation with BCR\/ABL1-transduced cells, and a genetic model constructed by crossing\n                    <jats:italic>Parp1<\/jats:italic>\n                    knockout mice with BCR\/ABL1 transgenic mice. The results showed that a PARPi, olaparib, attenuates BCR\/ABL1-mediated leukemogenesis. One possible mechanism underlying PARPi-dependent inhibition of leukemogenesis is increased interferon signaling via activation of the cGAS\/STING pathway. This is compatible with the use of interferon as a first-line therapy for CML. Because tyrosine kinase inhibitor (TKI) monotherapy does not completely eradicate leukemic cells in all patients, combined use of PARPi and a TKI is an attractive option that may eradicate CML stem cells.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-33852-2","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T08:32:19Z","timestamp":1683707539000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting Poly(ADP)ribose polymerase in BCR\/ABL1-positive cells"],"prefix":"10.1038","volume":"13","author":[{"given":"Haruka","family":"Hiroki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Piao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Namikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuko","family":"Masutani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshi","family":"Akahane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Inukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Morio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"33852_CR1","first-page":"930","volume":"18","author":"D Cilloni","year":"2012","unstructured":"Cilloni, D. & Saglio, G. 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The downregulation of BAP1 expression by BCR-ABL reduces the stability of BRCA1 in chronic myeloid leukemia. Exp Hematol 43, 775\u2013780 (2015).","journal-title":"Exp Hematol"},{"key":"33852_CR7","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nature03445","volume":"434","author":"H Farmer","year":"2005","unstructured":"Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917\u2013921 (2005).","journal-title":"Nature"},{"key":"33852_CR8","doi-asserted-by":"publisher","first-page":"djx62","DOI":"10.1093\/jnci\/djx062","volume":"109","author":"M Takagi","year":"2017","unstructured":"Takagi, M. et al. Loss of DNA damage response in neuroblastoma and utility of a PARP inhibitor. 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