MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias.
Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673-676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253-258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia.
Calin
George Adrian
GA
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Liu
Chang-Gong
CG
Sevignani
Cinzia
C
Ferracin
Manuela
M
Felli
Nadia
N
Dumitru
Calin Dan
CD
Shimizu
Masayoshi
M
Cimmino
Amelia
A
Zupo
Simona
S
Dono
Mariella
M
Dell'Aquila
Marie L
ML
Alder
Hansjuerg
H
Rassenti
Laura
L
Kipps
Thomas J
TJ
Bullrich
Florencia
F
Negrini
Massimo
M
Croce
Carlo M
CM
D001402:B-Lymphocytes; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D020869:Gene Expression Profiling / Q000379:methods*; D005803:Genes, Immunoglobulin; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis*; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D051746:ZAP-70 Protein-Tyrosine Kinase
D035683:MicroRNAs; D015345:Oligonucleotide Probes; D012334:RNA, Neoplasm; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human