Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia.
MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that modulate the expression of genes at the posttranscriptional level. These small molecules have been shown to be involved in cancer, apoptosis, and cell metabolism. In the present study we provide an informative profile of the expression of miRNAs in primary chronic lymphocytic leukemia (CLL) cells using 2 independent and quantitative methods: miRNA cloning and quantitative real-time-polymerase chain reaction (qRT-PCR) of mature miRNAs. Both approaches show that miR-21 and miR-155 are dramatically overexpressed in patients with CLL, although the corresponding genomic loci are not amplified. miR-150 and miR-92 are also significantly deregulated in patients with CLL. In addition, we detected a marked miR-15a and miR-16 decrease in about 11% of cases. Finally, we identified a set of miRNAs whose expression correlates with biologic parameters of prognostic relevance, particularly with the mutational status of the IgV(H) genes. In summary, the results of this study offer for the first time a comprehensive and quantitative profile of miRNA expression in CLL and their healthy counterpart, suggesting that miRNAs could play a primary role in the disease itself.
Fulci
Valerio
V
Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma La Sapienza, Rome, Italy.
Chiaretti
Sabina
S
Goldoni
Marina
M
Azzalin
Gianluca
G
Carucci
Nicoletta
N
Tavolaro
Simona
S
Castellano
Leandro
L
Magrelli
Armando
A
Citarella
Franca
F
Messina
Monica
M
Maggio
Roberta
R
Peragine
Nadia
N
Santangelo
Simona
S
Mauro
Francesca Romana
FR
Landgraf
Pablo
P
Tuschl
Thomas
T
Weir
David B
DB
Chien
Minchen
M
Russo
James J
JJ
Ju
Jingyue
J
Sheridan
Robert
R
Sander
Chris
C
Zavolan
Mihaela
M
Guarini
Anna
A
Foà
Robin
R
Macino
Giuseppe
G
D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D005821:Genetic Techniques; D016678:Genome; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D007136:Immunoglobulins; D035683:MicroRNAs; D051746:ZAP-70 Protein-Tyrosine Kinase