THE A-MYB TRANSCRIPTION FACTOR IN NEOPLASTIC AND NORMAL B-CELLS

The myb family of transcription factors has been strongly implicated i n the regulation of cell growth and differentiation in the haematopoie tic system. The v-myb oncogene, carried by avian defective retroviruse s, causes leukaemias in the chicken and transforms haematopoietic cell s in vitro. Its normal cellular equivalent c-myb, has been shown to pr omote the proliferation and block the differentiation of haematopoieti c cells in several experimental models and is required for fetal haema topoiesis. Two other members of the family have been cloned more recen tly, A-myb and B-myb, which show sequence homology with c-myb in sever al domains, of which the DNA binding domain as well as other regulator y domains. Both have been shown to be transcription factors. B-myb is also involved in the control of proliferation and differentiation, but , unlike c-myb, it is expressed in many cell types. The third member o f the family, A-myb, shows the most restricted pattern of expression, suggesting a very specific role for this transcription factor. A-myb i s expressed in a subpopulation of normal B lymphocytes activated in vi vo and localised in the germinal center of peripheral lymphoid organs and is not detected at significant levels in all other mature or immat ure haematopoietic populations studied, including bone marrow cells, T lymphocytes, granulocytes, monocytes, either at rest or after in vitr o activation. These studies indicate that A-myb plays a role during a narrow window of normal B cell differentiation. A-myb expression has a lso been studied in a wide range of neoplastic B cells, representing t he whole spectrum of B cell differentiation. A-myb is strongly express ed in Burkitt's lymphomas (BL) and slg(+) B-acute lymphoblastic leukae mias (B-ALL) and not in all other leukaemias/lymphomas tested with the exception of a subset of CLL (about 25% of cases). It is intriguing t hat the A-myb genome has been localised relatively close to the c-myc gene on chromosome 8, suggesting that the c-myc translocation in BL an d B-ALL may affect A-myb transcription. Studies are in progress to inv estigate the functional relationship between A-myb and c-myc, particul arly in the context of BL cells and to determine whether A-myb is dere gulated in these cells.