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Lack of somatic hypermutation of IG VH genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene

Abstract

The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is a rare but recurrent chromosomal aberration in B-cell malignancies. Hitherto, juxtaposition of BCL11A and IGH has only been described in B-cell chronic lymphocytic leukemia (B-CLL) and immunocytoma. As subgroups of B-CLL can be distinguished by the pattern of somatic mutation of immunoglobulin variable (V) genes we investigated four lymphomas with IGH/BCL11A involvement for IGH hypermutation. Clonal VH gene rearrangements were amplified; in all four cases, sequencing of the amplificates revealed the rearranged VH genes to lack somatic mutations. These results suggest that t(2;14)(p13;q32.3) is associated with a subset of B-CLL/immunocytoma characterized by non-mutated IG genes deriving from pre-germinal center B cells. As the translocations in both informative cases are targeted to the switch regions of the IGG2 gene, which is mainly used in T cell-independent immune responses, these translocations presumably occurred in activated B cells in the course of T cell-independent immune responses outside the germinal center.

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Acknowledgements

We thank Michaela Fahrig for excellent technical assistance. This work was supported by grants from the Deutsche Krebshilfe, NIH grant CA92318, and the Deutsche Forschungsgemeinschaft (through SFB502 and a Heisenberg award to RK).

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Küppers, R., Sonoki, T., Satterwhite, E. et al. Lack of somatic hypermutation of IG VH genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene. Leukemia 16, 937–939 (2002). https://doi.org/10.1038/sj.leu.2402480

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