What retroviruses teach us about the involvement of c-Myc in leukemias and lymphomas

• Published in: Leukemia Vol. 16; no. 6; pp. 1086 - 1098
• Main Authors: DUDLEY, J. P, MERTZ, J. A, RAJAN, L, LOZANO, M, BROUSSARD, D. R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.06.2002; Nature Publishing Group
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Apoptosis; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; c-Myc protein; Chromosomes; Cloning; Disease Progression; Enhancers; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Hematologic and hematopoietic diseases; Humans; Immunoglobulins; Insertion; Leukemia; Leukemia - genetics; Leukemia - metabolism; Leukemia - virology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Long terminal repeat; Lymphocytes; Lymphoma; Lymphoma - genetics; Lymphoma - metabolism; Lymphoma - virology; Lymphomas; Medical sciences; Myc protein; Oncogenes; Physiological aspects; Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - physiology; Proto-oncogenes; Retroviridae - genetics; Retrovirus; Retroviruses; Risk factors; Terminal Repeat Sequences; Transcription; Transcription factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transgenic animals; Tumors; Virus Integration; United States; Human; Leukemia; Retroviridae; Malignant hemopathy; Review; Carcinogenesis; Lymphoma; Infection; Virus; Lymphoproliferative syndrome; C-Onc gene; Viral disease; Genetics; Protooncogene
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402451

Overexpression of the cellular oncogene c-Myc frequently occurs during induction of leukemias and lymphomas in many species. Retroviruses have enhanced our understanding of the role of c-Myc in such tumors. Leukemias and lymphomas induced by retroviruses activate c-Myc by: (1) use of virally specified proteins that increase c-Myc transcription, (2) transduction and modification of c-Myc to generate a virally encoded form of the gene, v-Myc, and (3) proviral integration in or near c-Myc. Proviral integrations elevate transcription by insertion of retroviral enhancers found in the long terminal repeat (LTR). Studies of the LTR enhancer elements from these retroviruses have revealed the importance of these elements for c-Mycactivation in several cell types. Retroviruses also have been used to identify genes that collaborate with c-Myc during development and progression of leukemias and lymphomas. In these experiments, animals that are transgenic for c-Mycoverexpression (often in combination with the overexpression or deletion of known proto-oncogenes) have been infected with retroviruses that then insertionally activate novel co-operating cellular genes. The retrovirus then acts as a molecular 'tag' for cloning of these genes. This review covers several aspects of c-Myc involvement in retrovirally induced leukemias and lymphomas.