13q, 11q Derive from Common Ancestral Area in Zebrafish

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Br J Haematol. 2007 Jun;137(5):443-53.

The 13q and 11q B-cell chronic lymphocytic leukaemia-associated

regions derive from a common ancestral region in the zebrafish.

Auer RL, Riaz S, Cotter FE.

Centre for Haematology, Institute of Cell and Molecular Science,

Barts & The London, Queen 's School of Medicine, London, UK.

Loss of the long arm of chromosomes 11 and 13 is the most consistent

cytogenetic abnormalities for patients with B-cell chronic

lymphocytic leukaemia (B-CLL). They suggest the presence of as yet

unidentified tumour suppressor genes within well-defined minimal-

deleted regions (MinDRs).

We have identified 38 orthologues of the human genes in MinDRs in

zebrafish cDNA and syntenic regions for the human deletions in the

zebrafish genome. One region on chromosome 9 in the zebrafish genome

is of potential interest. Within chromosome 9, five genes and two

microRNAs were identified with shared synteny to the MinDRs in B-CLL

(two genes to human chromosome 11, three to human chromosome 13 and

two chromosome 13 microRNAs). The critical region on zebrafish

chromosome 9 maps to the MinDR for both human chromosomes,

suggesting a common ancestry for B-CLL tumour suppressor genes.

Target-selected mutagenesis to identify zebrafish mutants with knock-

outs of genes in this region will allow analysis of their in vivo

potential for lymphoproliferation and may define causative genes for

B-CLL within human chromosomes 11q and 13q.

Our study provides an explanation for involvement of both 11q and

13q in B-CLL and the potential to develop animal models for this

common lymphoproliferative disorder.

PMID: 17488487 [PubMed - in process]