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MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family

Oncogene volume 28, pages 1274–1279 (2009)Cite this article

Abstract

Signals that control the fine balance between cell death and cell survival are altered during tumorigenesis. Understanding the mechanisms by which this balance is perturbed, leading to excessive cell survival, is important for designing effective therapies. Proteins belonging to the B-cell lymphoma (BCL) family are known to regulate death responses to apoptotic signals, especially those originating within cells. A subset of BCL family members capable of inhibiting cell death is known to contribute to tumorigenesis; however, it is not known whether all six antiapoptotic BCL family members play a causal role in tumor development. Using a mouse model of MYC-driven leukemia, we showed that, in addition to the well characterized BCL2 and BCLxl (BCL2L1), the other four family members—BCLw (BCL2L2), BCLb (BCL2L10), BFL1 (BCL2A1) and MCL1—also cooperate with MYC to accelerate leukemogenesis. In addition, high levels of each family member are found in either solid human tumors or cell lines derived from human leukemias or lymphomas.

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Acknowledgements

We thank members of the Varmus laboratory, especially G Sanchez, A Giannakou and MA Melnick, for expert handling of the mouse colony, including genotyping, and for performing immunohistochemistry on embedded tissue sections. Funding for this project was provided, in part, by NIH P01 2PO1CA094060-06A1 to HEV.

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  1. Department of Cancer Genetics and Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    L J Beverly & H E Varmus

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  1. L J Beverly
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  2. H E Varmus
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Correspondence to L J Beverly.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Beverly, L., Varmus, H. MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family. Oncogene 28, 1274–1279 (2009). https://doi.org/10.1038/onc.2008.466

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