title: Association of human leukocyte antigen ancestral haplotype 8.1 with adverse outcome of non-Hodgkin's lymphoma.
abstract: Previous reports have implicated the tumor necrosis factor (TNF-308) locus to non-Hodgkin's lymphoma (NHL) outcome. The purpose of the study was to examine other chromosome components of the HLA 8.1 ancestral haplotype (AH) and their relation to the clinical course of NHL. HLA class I, II, TNF-308, and lymphotoxin alpha (LTA+252) alleles were analyzed in 154 newly diagnosed NHL patients. Three locus haplotypes were inferred from the unphased genotypes by a Bayesian implementation of the expectation maximization (EM) algorithm using the PHASE 2.1 program. TNF-308A was the only allele associated with fever, poor performance status, elevated beta2-microglobulin, TNF and its p75 receptor plasma levels. Although TNF-308A was in strong linkage disequilibrium with the remaining alleles of 8.1 AH, only HLA-A*01 and HLA-B*08 showed association with prognostic variables. A part of 8.1 AH (A*01-B*08-TNF-308A) was predictive for shorter freedom from progression and overall survival (RR=2.47, P=0.041; RR=3.15; P=0.0049), an association that was stronger than TNF-308A alone and independent from International Prognostic Index (RR=1.55, P<0.001; RR=2.36; P<0.0001). A*01-B*08-TNF-308A fragment of 8.1 AH remained an independent predictive factor in a multivariate model. We conclude that 8.1 AH is an important contributor to NHL outcome. In contrast to A*01-B*08-TNF(-308A, the remaining alleles (Cw*07, DRB1*03, LTA+252G) associated with the 8.1 AH seem to be its passive components.
authors.affiliation: Institute of Haematology and Blood Transfusion, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Nowak
authors.forename: Ewa
authors.initials: E
authors.lastname: Kalinka-Warzocha
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Juszczynski
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Bilinski
authors.forename: Renata
authors.initials: R
authors.lastname: Mika-Witkowska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zajko
authors.forename: Jacques
authors.initials: J
authors.lastname: Bienvenu
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
mesh_terms: D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics*; D015788:HLA-A1 Antigen; D015236:HLA-C Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017384:Sequence Deletion; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015788:HLA-A1 Antigen; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha