title: CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia.
abstract: We recently identified a disease-specific gene CLLU1 in chronic lymphocytic leukemia (CLL) and also demonstrated that high CLLU1 expression levels predict poor clinical outcome. To validate this finding, we measured CLLU1 mRNA expression levels by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 175 patients with CLL. Analyses of IgV(H) mutational status, ZAP-70 expression, CD38 expression, and chromosomal aberrations were also performed. High levels of CLLU1 expression were associated with shorter overall survival (P < .001), with a 7% increase in risk of early death by each doubling of the CLLU1 expression level. Stratification for age at diagnosis demonstrated a strong prognostic significance of CLLU1 expression in patients younger than 70 years (P < .001), but not in patients aged 70 or older (P = .61). The prognostic significance of IgV(H) mutational status and ZAP-70 expression had a similar age-dependent variation. Multivariate analysis in the younger age group showed that CLLU1 expression analysis added further prognostic information within all prognostic subgroups, with the exception of patients with unmutated IgV(H) CLL. Only CLLU1 expression and IgV(H) mutational status had independent predictive power. Thus, analysis of CLLU1 expression is highly applicable in risk prediction in CLL for patients of an age eligible for risk stratification.
authors.affiliation: The Leukemia Laboratory, Department of Hematology, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. par.josefsson@pc.dk
authors.forename: Pär
authors.initials: P
authors.lastname: Josefsson
authors.forename: Christian H
authors.initials: CH
authors.lastname: Geisler
authors.forename: Henrik
authors.initials: H
authors.lastname: Leffers
authors.forename: Jørgen H
authors.initials: JH
authors.lastname: Petersen
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Buhl
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011379:Prognosis; D062085:RNA, Long Noncoding; D012306:Risk; D016896:Treatment Outcome; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis
chemical_list: C510032:CLLU1 lncRNA, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1