A NOVEL ANTI-APOPTOSIS GENE, SURVIVIN, EXPRESSED IN CANCER AND LYMPHOMA

Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer(1) by facilitating the insurge nce of mutations and by promoting resistance to therapy(2). Despite th e identification of several new apoptosis inhibitors related to bcl-2( 2,3) or to the baculovirus IAP gene(4-9), it is not clear whether apop tosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibito r, designated survivin. Survivin contains a single baculovirus IAP rep eat and lacks a carboxyl-terminal RING finger. Present during fetal de velopment, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transform ed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in app roximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, i mmunoblastic), but not in low-grade lymphomas (lymphocytic). Recombina nt expression of survivin counteracts apoptosis of B lymphocyte precur sors deprived of interleukin 3 (IL-3). These findings suggest that apo ptosis inhibition may be a general feature of neoplasia and identify s urvivin as a potential new target for apoptosis-based therapy in cance r and lymphoma.