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ABSTRACT _Bcr-Abl_ tyrosine kinase activity is essential for the pathogenesis of chronic myeloid leukemia (CML). A number of _Bcr-Abl_ substrates have been identified, but it is not clear

which of these substrates are required for _Bcr-Abl_ to transform cells. The multifunctional protein c-Cbl is one of the most prominently tyrosine-phosphorylated proteins in

_Bcr-Abl_-expressing cells. Using cell lines and mice with homozygous disruption of the _c-CBL_ locus, we investigated the role of this protein for _Bcr-Abl_-driven transformation. We find

that although _c-Cbl_−/− fibroblast cell lines show a deficit in _Bcr-Abl_ transformation compared to wild-type (Wt) cells, this deficit was less pronounced in _c-Cbl_−/− B cells derived

from murine bone marrow. Most importantly, in a transplantation model of CML, _Bcr-Abl_ was capable of inducing fatal leukemia in mice in the absence of c-Cbl protein. Our results indicate

that c-Cbl is dispensable for _Bcr-Abl_-induced leukemogenesis in mice. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AN INSTRUCTIVE ROLE FOR INTERLEUKIN-7 RECEPTOR Α IN THE

DEVELOPMENT OF HUMAN B-CELL PRECURSOR LEUKEMIA Article Open access 03 February 2022 ACTIVATED INTERLEUKIN-7 RECEPTOR SIGNALING DRIVES B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN MICE Article 30

June 2021 CONSTITUTIVE ACTIVATION OF THE SRC-FAMILY KINASES FGR AND HCK ENHANCES THE TUMOR BURDEN OF ACUTE MYELOID LEUKEMIA CELLS IN IMMUNOCOMPROMISED MICE Article Open access 02 January

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Center for Cancer Research, 40 Ames Street, Cambridge, MA, 02139, USA AUTHORS AND AFFILIATIONS * Department of Cell and Developmental Biology, OR, USA Daniela M Dinulescu, Lisa J Wood, Lei

Shen, Michael W N Deininger & Brian J Druker * Division of Hematology/Oncology, Oregon Health & Science University Cancer Institute, Portland, 97239, OR, USA Daniela M Dinulescu, 

Lisa J Wood, Lei Shen, Michael W N Deininger & Brian J Druker * Department of Primary Care, Oregon Health & Science University School of Nursing, Portland, 97239, OR, USA Lisa J Wood

* Department of Pathology, VA Medical Center, Portland, 97239, OR, USA Marc Loriaux & Christopher L Corless * Department of Biology, Rosenstiel Basic Medical Sciences Research Center,

Brandeis University, Waltham, 02454, MA, USA Alec W Gross & Ruibao Ren Authors * Daniela M Dinulescu View author publications You can also search for this author inPubMed Google Scholar

* Lisa J Wood View author publications You can also search for this author inPubMed Google Scholar * Lei Shen View author publications You can also search for this author inPubMed Google

Scholar * Marc Loriaux View author publications You can also search for this author inPubMed Google Scholar * Christopher L Corless View author publications You can also search for this

author inPubMed Google Scholar * Alec W Gross View author publications You can also search for this author inPubMed Google Scholar * Ruibao Ren View author publications You can also search

for this author inPubMed Google Scholar * Michael W N Deininger View author publications You can also search for this author inPubMed Google Scholar * Brian J Druker View author publications

You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Brian J Druker. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Dinulescu, D., Wood, L., Shen, L. _et al._ _c-CBL_ is not required for leukemia induction by _Bcr-Abl_ in mice. _Oncogene_ 22, 8852–8860 (2003).

https://doi.org/10.1038/sj.onc.1206892 Download citation * Received: 11 September 2002 * Revised: 05 June 2003 * Accepted: 19 June 2003 * Published: 04 December 2003 * Issue Date: 04

December 2003 * DOI: https://doi.org/10.1038/sj.onc.1206892 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * _c-Cbl_ * _Bcr-Abl_ * leukemia *

CML