Untitled - Red Temática de investigación cooperativa en cáncer

P-30
GENETIC VARIANTS IN MIRNAS: NEW PREDICTIVE MARKERS IN THE
ORIGIN OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA
GUTIÉRREZ CAMINO A 1 , LÓPEZ LÓPEZ E 1 , GARCÍA-MIGUEL P 2 , SÁNCHEZ DE TOLEDO J 3 , CARBONÉ
BAÑERES A 4 , PIÑÁN MA 5 , GARCÍA DE ANDOIN N 6 , NAVAJAS A 5 , GARCÍA-ORAD A 1
1
UNIVERSIDAD DEL PAÍS VASCO, BILBAO (RD06/0020/0048)
2
HOSPITAL LA PAZ, MADRID (RD06/0020/0048)
3
HOSPITAL VALL D´HEBRÓN, BARCELONA (RD06/0020(1021)
4
HOSPITAL MIGUEL SERVET
5
HOSPITAL DE CRUCES, BILBAO (RD06/0020/0048)
6
HOSPITAL DONOSTIA, DONOSTIA (RD06/0020/0048)
Purpose: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children.
ALL develops during early life, and consequently, a strong genetic influence is expected.
In fact, several polymorphisms (SNPs) have been associated with ALL in previous GWAS.
MicroRNAs (miRNA) are non-coding RNAs that act as negative regulators of the expression
of other genes. Up to 171 deregulated miRNAs have been reported in children with ALL,
showing its importance in the disease.
Recent studies have provided evidence that SNPs in miRNAs and in genes of the processing
machinery of miRNAs migth be associated with risk of developing cancer, like SNP
rs11614913 in mir196a2 with the risk of lung and breast cancer and rs7813 in the GEMIN4
with ovaric and bladder cancer. Nevertheless, there are no studies in ALL risk.
The aim of this study was to evaluate the role of SNPs in both precursor miRNA and genes
related to miRNA biogenesis in susceptibility to pediatric ALL.
Material and Methods: We analyzed 238 childhood B-cell ALL patients during complete
remission and 352 healthy controls. 118 SNPs in miRNAs and miRNA biogenesis pathway
were studied with Taqman OpenArray platform.
Results: Eight polymorphisms were found to have significant associations (p>0,05) with
risk of childhood ALL. Five of them were located in the TNRC6B, CNOT6, DGCR8 and RNA-
SEN genes, which are involved in miRNA biogenesis. The other 3 SNPs were located in
miR-449b, miR-612 and miR-499.
Conclusion: Our results suggest that SNPs in miRNAs and miRNA biogenesis pathway
may affect childhood ALL susceptibility.
This project was supported by RETICS (RD/06/0020/0048), UPV/EHU (UFI 11/35) Basque
Government (GIC10/71, SAI10/03 and 2006111015) Jesús de Gangoiti Barrera Foundation.
Support by SGIker (UPV/EHU) is gratefully acknowledged.
P-31
ACTIVITY OF LENALIDOMIDE IN IN VITRO AND IN VIVO MODELS OF
BORTEZOMIB-RESISTANT MANTLE CELL LYMPHOMA
MOROS A 1 , SABORIT-VILLARROYA I 1 , PEREZ-GALAN P 1 , MARTINEZ A 2 , CAMPO E 2 , COLOMER D 2 ,
ROUE G 1
1
HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0014)
2
HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0039)
Mantle cell lymphoma (MCL) is an aggressive B lymphoid neoplasm genetically characterized
by the t(11;14)(q13;q32) leading to the overexpression of cyclin D1. Despite the
promising introduction of the proteasome inhibitor bortezomib in the clinical practice, not
all the patients respond and relapse frequently occurres. When comparing the behavior of
both bortezomib-resistant and bortezomib-sensitive cell lines in a xenotransplant mouse
model, we observed an increased tumorigenecity of bortezomib-resistant, suggesting a
major capacity of these tumors to interact with lymphoid microenvironment.
We assessed the activity in vitro and in vivo of the immunomoduladory drug lenalidomide
either alone or combined with the proteasome inhibitor in both bortezomib-resistant and
bortezomib-sensitive samples. Lenalidomide single agent was found to exert modest antitumoral
activity in 3/10 MCL cell lines, corresponding to those cells with either primary or
acquired resistance to the proteasome inhibitor.
Conversely, mice bearing bortezomib-resistant tumors and treated for 3 weeks with a 10-50
mg/kg/day regimen of lenalidomide, showed a 30 to 45% reduction in tumor burden when
compared to vehicle-treated group (p