The early transcription factor GATA-2 is expressed in classical Hodgkin's lymphoma

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL) are thought to be derived from germinal centre B-cells in almost all cases. However, expression profiling has revealed that HRS cells do not show a germinal centre B-cell-like phenotype. Although the nature of this aberrant phenotype and the underlying molecular mechanisms remain largely unknown, it has been reported that the activity of NOTCH1 plays an important role in the growth and survival of HRS cells. In some leukaemic cell lines, the effect of Notch signalling is mediated by the early transcription factor GATA-2. This and the fact that HRS cells lack expression of PU.1, which can repress Gata-2, led to an investigation of GATA-2 expression in HRS cells. GATA-2 expression was found in all the cHL-derived cell lines studied, but not in a Burkitt lymphoma-derived cell line. In addition, 50% of biopsies from patients with cHL contained GATA-2-expressing HRS cells. In contrast, neither normal germinal centre B-cells nor malignant cells of nodular lymphocyte-predominant Hodgkin's lymphoma, Burkitt lymphoma or diffuse large B-cell lymphoma expressed GATA-2. Thus, GATA-2 expression was found specifically in HRS cells of cHL, suggesting that GATA-2 is important in establishing the abnormal B-cell phenotype of HRS cells.