MiRNA expression profile of chronic lymphocytic leukemia patients with 13q deletion

被引:9
作者
Hernandez-Sanchez, Maria [1 ]
Rodriguez-Vicente, Ana E. [1 ]
Hernandez, Jose-Angel [2 ]
Lumbreras, Eva [1 ]
Sarasquete, Maria-Eugenia [1 ]
Martin, Ana-Africa [1 ]
Benito, Rocio [1 ]
Vicente-Gutierrez, Carlos [1 ]
Robledo, Cristina [1 ]
de las Heras, Natalia [3 ]
Rodriguez, Juan-Nicolas [4 ]
Alcoceba, Miguel [1 ]
Garcia de Coca, Alfonso [5 ]
Aguilar, Carlos [6 ]
Gonzalez, Marcos [1 ]
Hernandez-Rivas, Jesus-Maria [1 ]
机构
[1] Univ Salamanca, Hosp Univ Salamanca, CSIC, Hematol Dept,Ctr Invest Canc,IBSAL,IBMCC, Paseo San Vicente S-N, Salamanca 37007, Spain
[2] Univ Complutense Madrid, Hosp Univ Infanta Leonor, Dept Hematol, Madrid, Spain
[3] Hosp Virgen Blanca, Dept Hematol, Leon, Spain
[4] Hosp Juan Ramon Jimenez, Dept Hematol, Huelva, Spain
[5] Hosp Clin Univ, Dept Hematol, Valladolid, Spain
[6] Hosp Santa Barbara, Dept Hematol, Soria, Spain
关键词
miRNA; Array; 13q deletion; Expression; CLL; DOWN-REGULATION; BREAST-CANCER; MIR-155; SURVIVAL; DISEASE; CELLS; PROGNOSIS; LYMPHOMA; REVEALS; SUBSETS;
D O I
10.1016/j.leukres.2016.04.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Deletion 13q (13q-) is the most common cytogenetic aberration in chronic lymphocytic leukemia (CLL) and is associated with the most favorable prognosis as the sole cytogenetic abnormality. However, it is heterogeneous whereby CLL patients with higher percentages of 13q-cells (13q-H) have a more aggressive clinical course and a distinct gene expression profile. The microRNA (miRNA) expression profile of CLL gives additional biological and prognostic information, but its expression in 13q-CLL has not been examined in detail. The miRNA expression of clonal B cell lymphocytes (CD19+ cells) of 38 CLL patients and normal B cells of six healthy donors was analyzed. CLL patients with higher percentages of 13q-cells (>= 80%) showed a different level of miRNA expression from patients with lower percentages (<80%). Interestingly, miR-143 was downregulated and miR-155 was overexpressed in 13q-H. This deregulation affected important validated target genes involved in apoptosis (BCL2, MDM2, TP53INP1) and proliferation (KRAS, PI3K-AKT signaling), that could lead to decreased apoptosis and increased proliferation in 13q-H patients. This study provides new evidence about the heterogeneity of the 13q deletion in CLL patients, showing that miRNA regulation could be involved in several significant pathways deregulated in CLL patients with a high number of losses in 13q. (C) 2016 Published by Elsevier Ltd.
引用
收藏
页码:30 / 36
页数:7
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[1]   Downregulation of microRNAs-143 and-145 in B-cell malignancies [J].
Akao, Yukihiro ;
Nakagawa, Yoshihito ;
Kitade, Yukio ;
Kinoshita, Tomohiro ;
Naoe, Tomoki .
CANCER SCIENCE, 2007, 98 (12) :1914-1920
[2]   Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia [J].
Binet, JL ;
Caligaris-Cappio, F ;
Catovsky, D ;
Cheson, B ;
Davis, T ;
Dighiero, G ;
Döhner, H ;
Hallek, M ;
Hillmen, P ;
Keating, M ;
Montserrat, E ;
Kipps, TJ ;
Rai, K .
BLOOD, 2006, 107 (03) :859-861
[3]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193
[4]   The role of Bcl-2 family proteins in chronic lymphocytic leukaemia [J].
Buggins, Andrea G. S. ;
Pepper, Chris J. .
LEUKEMIA RESEARCH, 2010, 34 (07) :837-842
[5]   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
[6]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[7]   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
[8]   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
[9]   Role of miR-143 targeting KRAS in colorectal tumorigenesis [J].
Chen, X. ;
Guo, X. ;
Zhang, H. ;
Xiang, Y. ;
Chen, J. ;
Yin, Y. ;
Cai, X. ;
Wang, K. ;
Wang, G. ;
Ba, Y. ;
Zhu, L. ;
Wang, J. ;
Yang, R. ;
Zhang, Y. ;
Ren, Z. ;
Zen, K. ;
Zhang, J. ;
Zhang, C-Y .
ONCOGENE, 2009, 28 (10) :1385-1392
[10]   Biallelic deletion 13q14.3 in patients with chronic lymphocytic leukemia:: cytogenetic, FISH and clinical studies [J].
Chena, Christian ;
Sanchez Avalos, Julio ;
Bezares, Raimundo F. ;
Arrossagaray, Guillermo ;
Turdo, Karina ;
Bistmans, Alicia ;
Slavutsky, Irma .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2008, 81 (02) :94-99