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

Correspondence: Dr LJ Beverly, Department of Cancer Genetics and Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 62, New York, NY, 10065, USA. E-mail: BeverlyL@mskcc.org

Received 23 September 2008; Revised 23 October 2008; Accepted 26 November 2008; Published online 12 January 2009.

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.