“…For example, B cells in which the c-myc oncogene has been transfected and hyper-expressed would die in low serum concentrations in vitro unless exposed to CD40L or to an agonistic CD40 mAb which are both capable of inducing the upregulation of bcl2 and possibly of other anti-apoptotic genes (Cutrona et al, 1995). These observations suggest that a number of signals, delivered either by contact with stromal cells or by cytokines, prevent the apoptosis of CD10-positive ALL cells in vivo and facilitate their proliferation (Welch et al, 1990;Manabe et al, 1992Manabe et al, , 1994Saeland et al, 1992;Campana et al, 1994;Murti et al, 1996;Nishigaki et al, 1997). In this regard, it is of note that previous studies demonstrated that the ability of ALL cells to survive when cultured on stromal cells was an accurate predictor of a negative clinical outcome irrespective of the cell proliferative ability in vitro, possibly underlying the value of the anti-apoptotic properties of the stromal cells in the survival/expansion of the malignant ALL cells (Campana et al, 1993;Coustan-Smith et al, 1996;Kumagai et al, 1996).…”