Abnormalities of the long arm of chromosome 6 are a common feature in various B-cell malignancies. However, in most cases the involved genes have not yet clearly been identified. We have molecularly characterized the recently established cell line BLUE-1 that has been derived from a relapsed sporadic Burkitt lymphoma. This cell lines carries a t(6;20)(q15;q11.2) rearrangement in addition to the typical t(8;14) with MYC-IgH fusion. The involved gene loci on chromosomes 6 and 20 were up to now unknown.

To identify the involved gene loci on both chromosomes we applied a sequential BAC clone mapping strategy. BAC RP11-243J16 clone (20q11.21, bp 29,756,679–29,925,538) was found to hybridize with der(6) as well as der(20). BAC RP1-104D1 (6q15, bp 91,001,943–91,064,406) also covered the breakpoint region. Two of the involved genes in this region are the transcription factor BACH2 (basic leucine zipper transcription factor 2) on 6q15 and BCL2L1 (BCL-X) on 20q11, a member of the BCL2 anti-apoptosis gene family. We hypothesized that these two genes could be involved and by testing different primer combinations were able to amplify a BACH2-BCL2 fusion mRNA transcript using RT-PCR. In this fusion transcript the first (non-coding) exon of BACH2 was fused to the second (partially coding) exon of BCL2L1 thus effectively placing the BCL2L1 gene under the control of the BACH2 promotor. Western blot analysis showed a strong expression of BCL2L1.

This is the first report of a fusion gene involving the genes BACH2 and BCL2L1. The prototype of the BCL2 family, BCL-2 on 18q21.3 is known to play a crucial role in various lymphomas but a clear role for the closely related BCL2L1 gene in lymphomas has not yet been established. BACH2 is known to be expressed in B-cells at various maturation stages and is believed to be involved in the machinery of class switch recombination (CSR). Bach2 −/− mice show increased IgM but decreased IgG and IgA levels and a deficient T cell-independent and T cell-dependent IgG response associated with defective CSR.

In summary, this molecularly characterized translocation provides a new tool for studying recurrent 6q aberrations in lymphomas and for the action of the BCL2L1 antiapoptosis gene.

Disclosures: No relevant conflicts of interest to declare.

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