{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:11:37Z","timestamp":1791277897696,"version":"4.1.0"},"reference-count":35,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The bcr\/abl fusion in chronic myelogenous leukemia (CML) creates a chimeric tyrosine kinase with dramatically different properties than intact c-abl. In P210 bcr\/abl, the bcr portion includes a coiled-coil oligomerization domain (amino acids 1-63) and a grb2-binding site at tyrosine 177 (Tyr177) that are critical for fibroblast transformation, but give variable results in other cell lines. To investigate the role of the coiled-coil domain and Tyr177 in promoting CML, 4 P210 bcr\/abl-derived mutants containing different bcr domains fused to abl were constructed. All 4 mutants, \u0394(1-63) bcr\/abl, (1-63) bcr\/abl, Tyr177Phe bcr\/abl, and (1-210) bcr\/abl exhibited elevated tyrosine kinase activity and conferred factor-independent growth in cell lines. In contrast, differences in the transforming potential of the 4 mutants occurred in our mouse model, in which all mice receiving P210 bcr\/abl-expressing bone marrow cells exclusively develop a myeloproliferative disease (MPD) resembling human CML. Of the 4 mutants assayed, only 1-210 bcr\/abl, containing both the coiled-coil domain and Tyr177, induced MPD. Unlike full-length P210, this mutant also caused a simultaneous B-cell acute lymphocytic leukemia (ALL). The other 3 mutants, (1-63) bcr\/abl, Tyr177Phe bcr\/abl, and \u0394(1-63) bcr\/abl, failed to induce an MPD but instead caused T-cell ALL. These results show that both the bcr coiled-coil domain and Tyr177 are required for MPD induction by bcr\/abl and provide the basis for investigating downstream signaling pathways that lead to CML.<\/jats:p>","DOI":"10.1182\/blood.v99.8.2957","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T18:33:52Z","timestamp":1034361232000},"page":"2957-2968","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":107,"title":["The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia\u2013like disease by bcr\/abl"],"prefix":"10.1182","volume":"99","author":[{"given":"Yiping","family":"He","sequence":"first","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Wertheim","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanwei","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli P.","family":"Miller","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick G.","family":"Karnell","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Choi","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibao","family":"Ren","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren S.","family":"Pear","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221011047200_B1","first-page":"1197","article-title":"A minute chromosome in human chronic granulocytic leukemia.","volume":"132","author":"Nowell","year":"1960","journal-title":"Science."},{"key":"2020021221011047200_B2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0092-8674(91)90521-Y","article-title":"The BCR gene encodes a novel serine\/threonine kinase activity within a single exon.","volume":"67","author":"Maru","year":"1991","journal-title":"Cell."},{"key":"2020021221011047200_B3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0959-437X(05)80338-7","article-title":"Abl tyrosine kinase in signal transduction and cell-cycle regulation.","volume":"3","author":"Wang","year":"1993","journal-title":"Curr Opin Genet 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