Poster abstracts

Poster number 64 submitted by Natalya Nazaryan

Investigation of Dleu7 role as a tumor suppressor in CLL in vivo

Natalya Nazaryan (MVIMG), Yuri Pekarsky (MVIMG)

Abstract:
B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world. It is biologically very heterozygous with highly variable clinical course. The most frequent chromosomal aberration in B-CLL is deletion of 13q14 found in over 50% of CLL cases. Earlier studies showed that miR-15a/16-1 cluster is located within the deleted region and is implicated in pathogenesis of CLL. Recent report by Ouilette et al. demonstrated that in addition to miR-15a/16-1 the deleted region also contains the Dleu7 gene, a possible tumor suppressor candidate. We previously found that Dleu7 functions as a potent NF-kB and NFAT signaling inhibitor via direct interaction and inhibition of TACI and BCMI and hence acts as tumor suppressor in CLL. To further prove tumor suppressor function of Dleu7, we created Dleu7 knockout mouse model using EIIA-Cre/LoxP system. Mice carrying LoxP-flanked Dleu7 were crossed with EIIA-Cre+ mice in order to obtain Dleu7-/- animals. FACS analysis of spleen lymphocytes showed an accumulation of B220+CD5+ B-cells, characteristic to human B-CLL phenotype.

References:
Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of
micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc
Natl Acad Sci U S A. 2002;99(24):15524-15529
Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek SN. Integrated
genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion
13q14. Cancer Res. 2008;68(4):1012-1021.
Alexey Palamarchuk1*, Alexey Efanov1*, Natalya Nazaryan1, Urmila
Santanam1, Hansjuerg Alder1, Laura Rassenti2, Thomas Kipps2, Carlo M.
Croce1 and Yuri Pekarsky. 13q14 deletions in CLL involve cooperating tumor suppressors. Blood 2010;115(19):3916-22

Keywords: CLL, Dleu7, knockout, tumor suppressor