Expression of wild-type p53 and bcl-2 family genes oscillates with recurrent remission and relapse in an unusual case of low-grade lymphoma

Downregulation of apoptosis has been proposed as a mechanism of clonal expa nsion in low-grade B cell neoplasms. We have previously described an unusua l case of CD5+ B cell lymphoma characterized by cycles of leukemic phase al ternating with spontaneous remission. In the present study, we examined the involvement of apoptosis-related proteins in the progression of this cycli c lymphoma ex vivo. During the leukemic phases, the clonal cells were activ ated blasts expressing elevated levels of wild-type (wt) p53, Bcl-2, Bcl-x( L), and Bar, while Bak expression increased during the decline of lymphocyt osis. Bar heterodimerized with Bcl-2 but not with Bcl-x(L). The anti-apopto tic Bcl-2/Bax heterodimers peaked during early leukemic phases and declined during regression. The elevation in Bcl-2, Bcl-x(L) and Bar expression dur ing early leukemic phases seems to result from cell activation since a simi lar increase was induced by activating the remission phase leukemic cells i n culture. The data suggest that wt p53, Bcl-x(L), and Bcl-2/Bax heterodime rs support the accumulation of activated leukemic cells during the leukemic phases, while Bar and Bak may be involved in their decline during regressi on. Copyright (C) 2000 S. Karger AG, Basel.