title: Expression and prognostic significance of survivin in de novo acute myeloid leukaemia.
abstract: Survivin is an inhibitor of apoptosis (programmed cell death) overexpressed in various human cancers, but undetectable in normal differentiated tissues. A potential distribution and prognostic significance of survivin in patients with de novo acute myeloid leukaemia (AML) was investigated. By immunofluorescence of bone marrow specimens and peripheral blood mononuclear cells, survivin was detected in 75 out of 125 interpretable AML cases (60%), with 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 granulocytic maturation (one out of five M/L0, 11 out of 22 M/L1 and 23 out of 28M/L2; P = 0.007 by the Fisher test). In 69 patients treated with the Acute Leukaemia French Association (ALFA) 9000 protocol, survivin expression was significantly associated with a lower WBC (P = 0.03 by the Mann-Whitney test) and favourable/intermediate cytogenetics (P= 0.03 by the Fisher test). There was no significant difference in complete remission rate or overall survival between survivin-positive and survivin-negative AML patients (P = 0.15 by the log-rank test). However, survivin expression became an independent negative prognostic factor for survival when adjusted with the Cox model for established prognostic factors in AML (cytogenetics, age and WBC) or for the ALFA 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 unfavourable prognostic factor of de novo AML and suggest a role for apoptosis inhibition in influencing disease outcome.
authors.affiliation: Department of Pathology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: C
authors.initials: C
authors.lastname: Adida
authors.forename: C
authors.initials: C
authors.lastname: Recher
authors.forename: E
authors.initials: E
authors.lastname: Raffoux
authors.forename: M T
authors.initials: MT
authors.lastname: Daniel
authors.forename: A L
authors.initials: AL
authors.lastname: Taksin
authors.forename: P
authors.initials: P
authors.lastname: Rousselot
authors.forename: F
authors.initials: F
authors.lastname: Sigaux
authors.forename: L
authors.initials: L
authors.lastname: Degos
authors.forename: D C
authors.initials: DC
authors.lastname: Altieri
authors.forename: H
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000737:chemistry*; D018572:Disease-Free Survival; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007951:Leukemia, Myeloid / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D007958:Leukocyte Count; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D011379:Prognosis; D011506:Proteins / Q000032:analysis*; D012044:Regression Analysis; D012074:Remission Induction; D018709:Statistics, Nonparametric; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D000077022:Survivin