MiRNA expression profile of chronic lymphocytic leukemia patients with 13q deletion.
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.
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
María
M
Hernández-Sánchez
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Ana E
AE
Rodríguez-Vicente
Hematology Department, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain.
José-Ángel
JÁ
Hernández
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Eva
E
Lumbreras
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
María-Eugenia
ME
Sarasquete
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Ana-África
AÁ
Martín
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Rocío
R
Benito
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Carlos
C
Vicente-Gutiérrez
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Cristina
C
Robledo
Hematology Department, Hospital Virgen Blanca, León, Spain.
Natalia de Las
Nde L
Heras
Hematology Department, Hospital Juan Ramón Jiménez, Huelva, Spain.
Juan-Nicolás
JN
Rodríguez
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Miguel
M
Alcoceba
Hematology Department, Hospital Clínico Universitario, Valladolid, Spain.
Alfonso García de
AG
Coca
Hematology Department, Hospital Santa Bárbara, Soria, Spain.
Carlos
C
Aguilar
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain.
Marcos
M
González
Hematology Department, Centro de Investigación del Cáncer, IBSAL, IBMCC, Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, Salamanca, Spain. Electronic address: jmhr@usal.es.
Jesús-María
JM
Hernández-Rivas
D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis
C542359:MIRN143 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
13q deletion; Array; CLL; Expression; miRNA