13q Deletion and New Gene E4.5, May be Involved in CLL

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Leuk Lymphoma. 2003 Sep;44(9):1579-85.

13q deletion in chronic lymphocytic leukemia: characterization of

E4.5, a novel chromosome condensation regulator-like guanine

nucleotide exchange factor.

Solomou EE, Sfikakis PP, Kotsi P, Papaioannou M, Karali V, Vervessou

E, Hoffbrand AV, Panayiotidis P.

First Department of Propedeutic Medicine, University of Athens

Medical School, Laikon General Hospital, 17, Agiou Thoma St., Goudi,

Athens, Greece.

We report the characterization of a new gene (E4.5) that maps at

chromosome band 13q14.3, a chromosomal area frequently deleted in

chronic lymphocytic leukemia (CLL) and in other lymphoid

malignancies.

E4.5 gene encodes for a 4 kb mRNA expressed in various tissues and

has an open reading frame of 531 amino acids. The predicted E4.5

protein shows strong homology with the human regulator of chromosome

condensation (RCC1) protein, the principal GTP exchange factor for

Ran protein. The E4.5 protein contains a BTB domain in its N-

terminus, a protein-protein interaction motif. Therefore, we propose

that E4.5 is a new member of the RCC1-related guanine nucleotide

exchange factor (GEF) family with potent interaction with other

proteins and unknown function. Until now, no tumor suppressor genes

have been mapped in the 13q14.3 minimal deleted region (MDR) in

patients with CLL.

It has been proposed that loss of the 13q14.3 MDR may contribute to

lymphoid neoplasia by altering the expression/function of genes

located on 13q14.3 outside the MDR. The E4.5 is one of these genes

with a potential role in the pathogenesis of CLL.

PMID: 14565662 [PubMed - in process]