Bcr-Abl has a greater intrinsic capacity than v-Abl to induce the neoplastic expansion of myeloid cells (original) (raw)

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Published: 14 December 2000

Oncogene volume 19, pages 6286–6296 (2000)Cite this article

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Abstract

The Bcr-Abl/p210 fusion protein plays a primary role in the pathogenesis of chronic myelogenous leukemia (CML). Abelson murine leukemia virus, which encodes v-Abl/p160, induces a pre-B cell leukemia/lymphoma in mice. It has been unclear whether the apparent specificity of these two abl oncogenes for myeloid versus lymphoid neoplasms is due to specific intrinsic properties of these Abl oncoproteins, or due to the properties of the target cells expressing them. We have recently shown that expression of Bcr-Abl in bone marrow cells by retroviral transduction efficiently induces a myeloproliferative disorder in mice resembling human CML. In this study, we compared Bcr-Abl/p210 and v-Abl/p160 in this mouse CML model. We found that early in the course of disease, both Bcr-Abl/p210 and v-Abl/p160 expanded early immature hematopoietic cells. Later Bcr-Abl/p210 selectively expanded myeloid cells while v-Abl/p160 primarily induced the rapid in vivo expansion of B lymphoblastic cells, along with a minor population of myeloid cells. In vitro, Bcr-Abl/p210 induced more growth of myeloid colonies from 5-fluorouracil treated bone marrow than v-Abl/p160. These results, obtained under equal bone marrow transduction/transplantation conditions, indicate that Bcr-Abl/p210 has a greater intrinsic capacity than v-Abl/p160 to induce the neoplastic growth of myeloid cells. In addition, we found that cultured cells expressing Bcr-Abl/p210 had more activated STAT5 than cells that expressed v-Abl/p160. This suggests that activation of STAT5 might be one part of the mechanism of abl oncogene disease specificity.

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Acknowledgements

We thank Xiaowu Zhang for his assistance, and Ben Hentel and Jonathan Schatz for their help in analysing mice and with flow cytometry. This work was supported by National Cancer Institute grant CA68008 (to R Ren). R Ren is a recipient of The Leukemia and Lymphoma Society Scholar Award.

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Department of Biology, Rosenstiel Basic Medical Sciences Research Center, MS029, Brandeis University, Waltham, MA 02454-9110, Massachusetts, USA
Alec W Gross & Ruibao Ren

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Alec W Gross
Ruibao Ren

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Gross, A., Ren, R. Bcr-Abl has a greater intrinsic capacity than v-Abl to induce the neoplastic expansion of myeloid cells.Oncogene 19, 6286–6296 (2000). https://doi.org/10.1038/sj.onc.1204023

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Received: 30 June 2000
Revised: 13 October 2000
Accepted: 18 October 2000
Published: 14 December 2000
Issue date: 14 December 2000
DOI: https://doi.org/10.1038/sj.onc.1204023