title: Serum levels of p55 and p75 soluble TNF receptors in adult acute leukaemia at diagnosis: correlation with clinical and biological features and outcome.
abstract: The tumour necrosis factor (TNF)/TNF-receptor (TNFR) complex plays a role in the growth of leukaemic cells. We retrospectively investigated the relationship between pretreatment serum concentration of soluble TNFR (p55- and p75-sTNFRs) and outcome in adult acute myeloid (AML 82 cases) and lymphoid (ALL 44 cases) leukaemia. Both sTNFRs were significantly higher in AML (p55-sTNFR 4.53 +/- 3.7, median 3.75; p75-sTNFR 6.51 +/- 5.25 ng/ml, median 4.72) and ALL sera (3.31 +/- 1.5, median 2.95; 5.30 +/- 2.3 ng/ml, median 4.56, respectively) than in controls (1.89 +/- 0.5, median 1.98; 2.22 +/- 0.8 ng/ml, median 2.37) (P < 0.01 for both sTNFRs). Fresh leukaemic cells expressed p55- and p75-sTNFRs, which were modulated and released into the supernatant (SN) following short-term in vitro culture, suggesting that in vivo sTNFRs were also leukaemia-derived. Whereas no correlation was observed between sTNFRs and outcome in ALL, in AML higher p55-sTNFR levels (> 3.75 ng/ml) were associated with shorter disease-free survival (DFS) (P = 0.006) and overall survival (OS) (P = 0.0004). At multivariate analysis p55-sTNFR was the most significant predictor of DFS (P = 0.006) and OS (P < 0.001). Our data suggest that the prognostic significance of p55-sTNFR in AML could be related to relevant biological features of AML blasts.
authors.affiliation: Department of Haematology, Verona University School of Medicine, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Vinante
authors.forename: A
authors.initials: A
authors.lastname: Rigo
authors.forename: C
authors.initials: C
authors.lastname: Tecchio
authors.forename: L
authors.initials: L
authors.lastname: Morosato
authors.forename: G
authors.initials: G
authors.lastname: Nadali
authors.forename: M M
authors.initials: MM
authors.lastname: Ricetti
authors.forename: M
authors.initials: M
authors.lastname: Krampera
authors.forename: E
authors.initials: E
authors.lastname: Zanolin
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: H
authors.initials: H
authors.lastname: Gallati
authors.forename: M
authors.initials: M
authors.lastname: Chilosi
authors.forename: G
authors.initials: G
authors.lastname: Pizzolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000628:therapy; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012189:Retrospective Studies; D012995:Solubility; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II