microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival.
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.
Rossi
Simona
S
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Shimizu
Masayoshi
M
Barbarotto
Elisa
E
Nicoloso
Milena S
MS
Dimitri
Federica
F
Sampath
Deepa
D
Fabbri
Muller
M
Lerner
Susan
S
Barron
Lynn L
LL
Rassenti
Laura Z
LZ
Jiang
Li
L
Xiao
Lianchun
L
Hu
Jianhua
J
Secchiero
Paola
P
Zauli
Giorgio
G
Volinia
Stefano
S
Negrini
Massimo
M
Wierda
William
W
Kipps
Thomas J
TJ
Plunkett
William
W
Coombes
Kevin R
KR
Abruzzo
Lynne V
LV
Keating
Michael J
MJ
Calin
George A
GA
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
D005819:Genetic Markers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
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