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

• Published in: Oncogene Vol. 28; no. 9; pp. 1274 - 1279
• Main Authors: Beverly, L J, Varmus, H E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.03.2009; Nature Publishing Group
• Subjects: Apoptosis; Apoptosis - genetics; B-cell lymphoma; Biological and medical sciences; Care and treatment; Cell Biology; Cell death; Cell physiology; Cell survival; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Cellular proteins; Cellular signal transduction; Fundamental and applied biological sciences. Psychology; Genes, myc; Genetic aspects; Genetics; Health aspects; Human Genetics; Humans; Internal Medicine; Leukemia, Myeloid - genetics; Leukemia, Myeloid - pathology; Leukemogenesis; Lymphocytes B; Lymphoma; Mcl-1 protein; Medicine; Medicine & Public Health; Molecular and cellular biology; Myc protein; Non-Hodgkin's lymphomas; Oncogene Proteins - physiology; Oncology; Physiological aspects; short-communication; Signal transduction; Tumorigenesis; United States; BCL2; BCLb; BCLw; BFL1; BCLxl; MCL1; C-Onc gene; Onc gene; Carcinogenesis; Protooncogene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2008.466

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.