To the genesis of Burkitt lymphoma: Regulation of apoptosis by EBNA-1 and SAP may determine the fate of Ig-myc translocation carrying B lymphocytes

Chromosomal translocations that juxtapose one of the three immunoglobulin loci to the c-myc protooncogene are the hallmark of Burkitt lymphomas (BLs), whether they carry the Epstein Barr Virus (EBV) or not. Ig/myc translocations occur as accidents of normal B lymphocyte differentiation. Unless protected, the translocation carrying cells are apoptosis prone. However, the high B cell stimulatory cytokine level found in the two BL prone conditions, in chronic hyperendemic malaria and HIV infection, may rescue them. X-linked lymphoproliferative disease (XLP) is due to the lack of functional SAP protein, a consequence of mutation or deletion of the SAP gene. We and others have shown that SAP is pro-apoptotic. Here we summarize our finding that 8 of 10 EBV carrying, but none of 9 EBV negative BL lines express SAP. We suggest that the apoptosis prone Ig/myc translocation carrying EBV negative precursors of BL can only grow into lymphomas if they do not express SAP. However, their EBV positive counterparts are permissive for SAP expression, due to the anti-apoptotic function of EBNA-1.