title: microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival.
abstract: Aberrant expression of microRNAs (miRNAs) has been associated with clinical outcome in patients with chronic lymphocytic leukemia (CLL). To identify a powerful and easily assessable miRNA bio-marker of prognosis and survival, we performed quantitative reverse-transcription polymerase chain reaction (qRT-PCR) profiling in 104 CLL patients with a well-defined chromosome 17p status, and we validated our findings with miRNA microarray data from an independent cohort of 80 patients. We found that miR-15a, miR-21, miR-34a, miR-155, and miR-181b were differentially expressed between CLLs with chromosome 17p deletion and CLLs with normal 17p and normal karyotype, and that miR-181b was down-regulated in therapy-refractory cases. miR-21 expression levels were significantly higher in patients with poor prognosis and predicted overall survival (OS), and miR-181b expression levels significantly predicted treatment-free survival. We developed a 21FK score (miR-21 qRT-PCR, fluorescence in situ hybridization, Karyotype) to stratify patients according to OS and found that patients with a low score had a significantly longer OS time. When we evaluated the relative power of the 21FK score with the most used prognostic factors, the score was the most significant in both CLL cohorts. We conclude that the 21FK score represents a useful tool for distinguishing between good-prognosis and poor-prognosis CLL patients.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Rossi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Elisa
authors.initials: E
authors.lastname: Barbarotto
authors.forename: Milena S
authors.initials: MS
authors.lastname: Nicoloso
authors.forename: Federica
authors.initials: F
authors.lastname: Dimitri
authors.forename: Deepa
authors.initials: D
authors.lastname: Sampath
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Barron
authors.forename: Laura Z
authors.initials: LZ
authors.lastname: Rassenti
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Hu
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000592:standards / Q000706:statistics & numerical data*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009710:Nucleotide Mapping; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
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