Universität zu Köln

Klymenko, T., 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). S. 364 - 376. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5551

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klymenko, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloehdorn, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahlo, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robrecht, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Akylzhanova, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cox, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Estenfelder, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Edelmann, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Strefford, J. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wojdacz, T. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cragg, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gribben, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-196575
DOI:	10.1038/leu.2017.255
Journal or Publication Title:	Leukemia
Volume:	32
Number:	2
Page Range:	S. 364 - 376
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5551
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; NUCLEAR LAMINA; GENE-EXPRESSION; MEMORY B; IMMUNOGLOBULIN GENES; PLASMA-CELLS; CLL8 TRIAL; HYPERMUTATION; CHROMATIN; AID Multiple languages Oncology; Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19657