MYB-INDUCED TRANSFORMATION

The c-myb protooncogene has been implicated in the development of avia n and murine hematopoietic neoplasms of the myeloid and lymphoid linea ges. The transcription factor encoded by this gene has a dual function in oncogenesis because it regulates genes that prevent apoptosis and genes involved in cellular proliferation. c-myb has repeatedly been a target of retroviral insertional mutagenesis. The most common mechanis m by which retroviruses activate c-myb's oncogenic potential is by pro viding transcriptional control that results in constitutive expression , a feature that is consistent with the demonstration that ectopic exp ression of c-myb can prevent growth arrest of differentiating hematopo ietic cells. In a less common mechanism of activation, carboxyl(C)-ter minal truncation renders the c-Myb protein more stable and active in t ranscriptional transactivation. Interestingly, the ability of v-Myb, a product of the avian myeloblastosis virus (AMV), to cause rapid trans formation of cells in vivo and in vitro can be explained by the combin ed effects of deregulated expression through the retroviral LTR, N- an d C-terminal truncation, and activating mutations in its DNA binding d omain. Although c-myb's involvement in human leukemia has been suggest ed, it has never been clearly established and should be investigated f urther.