Lamin B1 regulates somatic mutations and progression of B-cell malignancies

KLYMENKO, Tetyana, BLOEHDORN, J, BAHLO, J, ROBRECHT, S, AKYLZHANOVA, G, COX, K, ESTENFELDER, S, WANG, J, EDELMANN, J, STREFFORD, J C, WOJDACZ, T K, FISCHER, K, HALLEK, M, STILGENBAUER, S, CRAGG, M, GRIBBEN, J and BRAUN, A (2018). Lamin B1 regulates somatic mutations and progression of B-cell malignancies. Leukemia, 32 (2), 364-375. [Article]

Documents
17091:287918
[thumbnail of Klymenko-LaminB1RegulaesSomaticMutations(VoR).pdf]
Preview
PDF
Klymenko-LaminB1RegulaesSomaticMutations(VoR).pdf - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview
Abstract
Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy.
More Information
Statistics

Downloads

Downloads per month over past year

Metrics

Altmetric Badge

Dimensions Badge

Share
Add to AnyAdd to TwitterAdd to FacebookAdd to LinkedinAdd to PinterestAdd to Email

Actions (login required)

View Item View Item