{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:36:43Z","timestamp":1791067003784,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2011,9,23]],"date-time":"2011-09-23T00:00:00Z","timestamp":1316736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p>The p210<jats:italic>Bcr\/Abl<\/jats:italic> and p190<jats:italic>Bcr\/Abl<\/jats:italic> fusion oncoproteins are known to cause chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Bcr\/Abl phosphorylates several proteins that can lead to leukemogenesis. Crk\u2010associated substrate lymphocyte type (Cas\u2010L)\/human enhancer of filamentation\u20101 (HEF1)\/neural precursor cell expressed, developmentally down\u2010regulated 9 (NEDD9) is an adapter protein at focal adhesions known to be associated with solid tumor metastasis. Crk\u2010associated substrate lymphocyte type has also been reported to be tyrosine phosphorylated by p190<jats:italic>Bcr\/Abl<\/jats:italic>. We demonstrated that Cas\u2010L was expressed in murine granulocytes, as well as in lymphocytes, and that Cas\u2010L\u2010deficient (<jats:italic>Cas\u2010L<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) granulocytes had increased migratory activity and decreased adhesiveness. To examine whether Cas\u2010L was involved in leukemogenesis by p210<jats:italic>Bcr\/Abl<\/jats:italic>, we generated <jats:italic>Cas\u2010L<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> p210<jats:italic>Bcr\/Abl<\/jats:italic> transgenic mice. The mice displayed early development of myeloproliferative neoplasm seen in the chronic phase of CML, which resulted in the early death of the mice. Pathologically, increased infiltration of myeloid cells into several tissues was detected in the absence of Cas\u2010L. In a hematopoietic reconstitution assay, <jats:italic>Cas\u2010L<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> p210<jats:italic>Bcr\/Abl<\/jats:italic> transgenic cells showed a low population in the spleen, although only their myeloid cell population was normal. Thus, Cas\u2010L seems to regulate the progression of CML in a negative way, presumably by attenuating extramedullary hyperplasia. (<jats:italic>Cancer Sci<\/jats:italic> 2011; 102: 2109\u20132117)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2011.02066.x","type":"journal-article","created":{"date-parts":[[2011,8,17]],"date-time":"2011-08-17T00:40:24Z","timestamp":1313541624000},"page":"2109-2117","source":"Crossref","is-referenced-by-count":15,"title":["Crk\u2010associated substrate lymphocyte type regulates myeloid cell motility and suppresses the progression of leukemia induced by 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