BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model

Oncogene
F LinR Arlinghaus

Abstract

It is well accepted that the Bcr-Abl oncoprotein encoded by the Philadelphia chromosome is responsible for causing chronic myelogenous leukemia (CML). We have previously demonstrated that expression of Bcr interferes with the oncogenic effects of Bcr-Abl. To examine the effects of increased Bcr expression on Bcr-Abl oncogenic effects in a more physiological system, we tested the leukemogenic potential of a clone of K562 cells (K6 K562) containing an inducible BCR gene in NOD/scid mice. In this clone, the BCR gene was placed under the control of a tetracycline (Tet) repression system with a cytomegalovirus (CMV) promoter. Induction of exogenous Bcr protein by removal of Tet from the culture medium caused a dramatic increase in Bcr serine kinase activity, yielding predominantly phosphoserine Bcr, despite the presence of Bcr-Abl in the kinase reaction mixture. Prior to induction, the endogenous Bcr was predominantly in the phosphotyrosine form because of phosphorylation by Bcr-Abl, which we previously have shown suppresses Bcr serine/threonine kinase activity. Injection of K6 K562 cells into NOD/scid mice under conditions where BCR expression was suppressed resulted in death or terminal illness in 100% of the mice within 35 days a...Continue Reading

References

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May 15, 1997·Oncogene·G MaR B Arlinghaus
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Citations

Dec 4, 2003·Biochemical and Biophysical Research Communications·Asit K Chakraborty, Salil K Das
Jul 30, 2008·Oncogene·X LengR Arlinghaus
Oct 16, 2007·Oncogene·B PerazzonaR Arlinghaus
Sep 19, 2001·Current Opinion in Hematology·R A Van Etten
Apr 10, 2008·Leukemia & Lymphoma·Ralph Arlinghaus, Xiaohong Leng
Jan 31, 2006·FEBS Letters·Angelika Ress, Karin Moelling
Dec 30, 2014·Expert Opinion on Drug Delivery·Ana Tari Ashizawa, Jorge Cortes
Apr 7, 2009·Advances in Enzyme Regulation·Xiaohong LengRalph Arlinghaus
Oct 8, 2005·EMBO Reports·Angelika Ress, Karin Moelling
Jul 24, 2004·Hematology/oncology Clinics of North America·Robert L Ilaria
Mar 7, 2003·Current Biology : CB·Gwendolyn M MahonIan P Whitehead
Dec 27, 2005·Cell·Laxminarayana R DevireddyMichael R Green
Mar 1, 2005·Oncogene·Hui LinRalph Arlinghaus

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