{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:07:14Z","timestamp":1790478434468,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,7,31]]},"abstract":"<jats:p>\u03b2-Arrestins were initially discovered as negative regulators of G protein-coupled receptor signaling. Although \u03b2-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of \u03b2-arrestins in driving oncogenesis is not known. Here we have investigated the role of \u03b2-arrestin in hematologic malignancies and have found that although both \u03b2-arrestin1 and -2 are expressed in the hematopoietic system, loss of \u03b2-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of \u03b2-arrestin2 leads to a significant inhibition of \u03b2-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the \u03b2-arrestin2 mutant cells. These data cumulatively show that \u03b2-arrestin2 is essential for CML disease propagation and indicate that \u03b2-arrestins and the Wnt\/\u03b2-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance.<\/jats:p>","DOI":"10.1073\/pnas.1209815109","type":"journal-article","created":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T02:41:28Z","timestamp":1341542488000},"page":"12532-12537","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["\u03b2-Arrestin2 mediates the initiation and progression of myeloid leukemia"],"prefix":"10.1073","volume":"109","author":[{"given":"Mark","family":"Fereshteh","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of California, San Diego School of Medicine and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093; and"},{"name":"Department of Pharmacology and Cancer Biology,"},{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, San Diego School of Medicine and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093; 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