The 13q and 11q B-cell chronic lymphocytic leukaemia-associated regions derive from a common ancestral region in the zebrafish

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.