Deregulation of Aiolos expression in chronic lymphocytic leukemia is associated to epigenetic modifications

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Blank Deregulation of Aiolos expression in chronic lymphocytic leukemia is

associated to epigenetic modifications.

K Billot, J Soeur, F Chereau, I Arrouss, H Merle-Beral, ME Huang, D

Mazier, V Baud, and A Rebollo

Blood, December 7, 2010;

Hopital Pitie-Salpetriere, Universite Pierre et Marie Curie (UPMC) Paris

VI, INSERM, UMR-S 945, Paris, France;

Chronic lymphocytic leukemia (CLL) is characterized by a clonal

accumulation of mature neoplastic B cells that are resistant to apoptosis.

Aiolos, a member of the Ikaros family of zinc-finger transcription factors,

plays an important role in the control of mature B lymphocyte differentiation

and maturation. In this study, we showed that Aiolos expression is upregulated

in B-CLL cells. This overexpression does not implicate isoform imbalance or

disturbing Aiolos subcellular localization. The chromatin status at the Aiolos

promoter in CLL is defined by the demethylation of DNA and an enrichment of

euchromatin associated histone markers, such as the dimethylation of the lysine

4 on histone H3. These epigenetic modifications should allow its upstream

effectors, such as NF-?B, constitutively activated in CLL, to gain access to

promoter, resulting upregulation of Aiolos. To determine the consequences of

Aiolos deregulation in CLL, we analysed the effects of Aiolos overexpression or

downregulation on apoptosis. Aiolos is involved in cell survival, by regulating

the expression of some Bcl-2 family members. Our results strongly suggest that

Aiolos deregulation by epigenetic modifications may be a hallmark of CLL.

PMID: 21139082