{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:44:05Z","timestamp":1790160245797,"version":"4.1.0"},"reference-count":50,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,10,27]]},"abstract":"<jats:p>Chronic myeloid leukemia (CML) represents the first human malignancy successfully treated with a tyrosine kinase inhibitor (TKI; imatinib). However, early relapses and the emergence of imatinib-resistant disease are problematic. Evidence suggests that imatinib and other inhibitors may not effectively eradicate leukemic stem\/progenitor cells, and that combination therapy directed to complimentary targets may improve treatment. Abelson helper integration site 1 (Ahi-1)\/AHI-1 is a novel oncogene that is highly deregulated in CML stem\/progenitor cells where levels of BCR-ABL transcripts are also elevated. Here, we demonstrate that overexpression of Ahi-1\/AHI-1 in murine and human hematopoietic cells confer growth advantages in vitro and induce leukemia in vivo, enhancing effects of BCR-ABL. Conversely, RNAi-mediated suppression of AHI-1 in BCR-ABL\u2013transduced lin\u2212CD34+ human cord blood cells and primary CML stem\/progenitor cells reduces their growth autonomy in vitro. Interestingly, coexpression of Ahi-1 in BCR-ABL\u2013inducible cells reverses growth deficiencies exhibited by BCR-ABL down-regulation and is associated with sustained phosphorylation of BCR-ABL and enhanced activation of JAK2\u2013STAT5. Moreover, we identified an AHI-1\u2013BCR-ABL\u2013JAK2 interaction complex and found that modulation of AHI-1 expression regulates phosphorylation of BCR-ABL and JAK2\u2013STAT5 in CML cells. Importantly, this complex mediates TKI response\/resistance of CML stem\/progenitor cells. These studies implicate AHI-1 as a potential therapeutic target downstream of BCR-ABL in CML.<\/jats:p>","DOI":"10.1084\/jem.20072316","type":"journal-article","created":{"date-parts":[[2008,10,21]],"date-time":"2008-10-21T00:45:28Z","timestamp":1224549928000},"page":"2657-2671","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem\/progenitor cells"],"prefix":"10.1084","volume":"205","author":[{"given":"Liang L.","family":"Zhou","sequence":"first","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Ringrose","sequence":"additional","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"DeGeer","sequence":"additional","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Kennah","sequence":"additional","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann E.-J.","family":"Lin","sequence":"additional","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Sheng","sequence":"additional","affiliation":[{"name":"2Department of Human Genetics, Emory University, Atlanta, GA 30322"},{"name":"3Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"2Department of Human Genetics, Emory University, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Turhan","sequence":"additional","affiliation":[{"name":"4Department of Hematology, University of Poitiers EA3805, 86021 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver V5Z 1L3, BC, Canada"},{"name":"5Department of Medical Genetics, University of British Columbia, Vancouver V5Z 1L3, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,10,20]]},"reference":[{"key":"2023072516120101300_BIB1","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMra020777","volume":"349","year":"2003","journal-title":"N. 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