Expression and prognostic significance of survivin in de novo acute myeloid leukaemia

Survivin is an inhibitor of apoptosis (programmed cell death) overexpressed in Various human cancers, but undetectable in normal differentiated tissue s. A potential distribution and prognostic significance of survivin in pati ents with de novo acute myeloid leukaemia (AML) was investigated. By immuno fluoresence of bone-marrow specimens and peripheral blood mononuclear cells , survivin was detected in 75 out of 125 interpretable AML cases (60%), wit h reactivity in 50-90% of AML cells. Survivin expression correlated with a lower white blood cell count (WBC) (P = 0.008 by the Mann-Whitney test) and was associated, in the 55 cases of FAB M0/M1/M2, with leukaemic granulocyt ic maturation tone out of five M/LO, 11 out of 22 M/LI and 23 out of 28M/L2 ; P = 0.007 by the Fisher test). In 69 patients treated with the Acute Leuk aemia French Association (ALFA) 9000 protocol, survivin expression was sign ificantly associated with a lower WBC (P = 0.03 by the Mann-Whitney test) a nd favourable/intermediate cytogenetics (P=0.03 by the Fisher test). There was no significant difference in complete remission rate or overall surviva l between survivin-positive and survivin-negative AML patients (P=0.15 by t he log-rank test). However survivin expression became an independent negati ve prognostic factor for survival when adjusted with the Cox model for esta blished prognostic factors in AML (cytogenetics, age and WBC) or for the AL FA 9000 treatment arm (RR = 2.8 and P = 0.026, by the likelihood-ratio test ). These data suggest that survivin expression may be considered as a new u nfavourable prognostic factor of de novo AML and suggest a role for apoptos is inhibition in influencing disease outcome.