Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia

被引:380
作者
Fulci, Valerio
Chiaretti, Sabina
Goldoni, Marina
Azzalin, Gianluca
Carucci, Nicoletta
Tavolaro, Simona
Castellano, Leandro
Magrelli, Armando
Citarella, Franca
Messina, Monica
Maggio, Roberta
Peragine, Nadia
Santangelo, Simona
Mauro, Francesca Romana
Landgraf, Pablo
Tuschl, Thomas
Weir, David B.
Chien, Minchen
Russo, James J.
Ju, Jingyue
Sheridan, Robert
Sander, Chris
Zavolan, Mihaela
Guarini, Anna
Foa, Robin
Macino, Giuseppe
机构
[1] Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Rome, Italy
[2] Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Sez Ematol, Rome, Italy
[3] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA
[4] Columbia Univ, Genome Ctr, New York, NY 10027 USA
[5] Columbia Univ, Dept Chem Engn, New York, NY 10027 USA
[6] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA
[7] Univ Basel, Biozentrum, CH-4003 Basel, Switzerland
关键词
D O I
10.1182/blood-2006-12-062398
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that modulate the expression of genes at the post-transcriptional 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.
引用
收藏
页码:4944 / 4951
页数:8
相关论文
共 44 条
[1]   Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].
Calin, GA ;
Dumitru, CD ;
Shimizu, M ;
Bichi, R ;
Zupo, S ;
Noch, E ;
Aldler, H ;
Rattan, S ;
Keating, M ;
Rai, K ;
Rassenti, L ;
Kipps, T ;
Negrini, M ;
Bullrich, F ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529
[2]   A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia [J].
Calin, GA ;
Ferracin, M ;
Cimmino, A ;
Di Leva, G ;
Shimizu, M ;
Wojcik, SE ;
Iorio, MV ;
Visone, R ;
Sever, NI ;
Fabbri, M ;
Iuliano, R ;
Palumbo, T ;
Pichiorri, F ;
Roldo, C ;
Garzon, R ;
Sevignani, C ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1793-1801
[3]   MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias [J].
Calin, GA ;
Liu, CG ;
Sevignani, C ;
Ferracin, M ;
Felli, N ;
Dumitru, CD ;
Shimizu, M ;
Cimmino, A ;
Zupo, S ;
Dono, M ;
Dell'Aquila, ML ;
Alder, H ;
Rassenti, L ;
Kipps, TJ ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) :11755-11760
[4]   A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA) [J].
Castoldi, M ;
Schmidt, S ;
Benes, V ;
Noerholm, M ;
Kulozik, AE ;
Hentze, MW ;
Muckenthaler, MU .
RNA, 2006, 12 (05) :913-920
[5]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[6]   MicroRNAs modulate hematopoietic lineage differentiation [J].
Chen, CZ ;
Li, L ;
Lodish, HF ;
Bartel, DP .
SCIENCE, 2004, 303 (5654) :83-86
[7]   Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis [J].
Cheng, AM ;
Byrom, MW ;
Shelton, J ;
Ford, LP .
NUCLEIC ACIDS RESEARCH, 2005, 33 (04) :1290-1297
[8]   miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[9]   Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice [J].
Costinean, S ;
Zanesi, N ;
Pekarsky, Y ;
Tili, E ;
Volinia, S ;
Heerema, N ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (18) :7024-7029
[10]   ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia [J].
Crespo, M ;
Bosch, F ;
Villamor, N ;
Bellosillo, B ;
Colomer, D ;
Rozman, M ;
Marcé, S ;
López-Guillermo, A ;
Campo, E ;
Montserrat, E .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (18) :1764-1775