Universität zu Köln

Knittel, Gero, Liedgens, Paul, Korovkina, Darya, Pallasch, Christian P. ORCID: 0000-0001-5675-6905 and Reinhardt, Hans Christian (2016). Rewired NF kappa B signaling as a potentially actionable feature of activated B-cell-like diffuse large B-cell lymphoma. Eur. J. Haematol., 97 (6). S. 499 - 511. HOBOKEN: WILEY-BLACKWELL. ISSN 1600-0609

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Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma in the Western world and remains a clinical challenge. Two types of DLBCL are distinguishable, namely a germinal center B-cell-like phenotype (GCB) and an activated B-cell-like phenotype (ABC). Particularly ABC-DLBCL is difficult to treat, as this subentity typically displays resistance against frontline chemo-immune therapy. Through the availability of novel experimental technologies, such as next-generation sequencing and cutting-edge mouse models, we recently caught an unprecedentedly detailed glimpse at the genomic and biological features of ABC-DLBCL. Currently, a picture is emerging which suggests that ABC-DLBCL critically depends on sustained activity of the NF kappa B pathway, which, among others, is achieved through numerous distinct genetic aberrations, including CD79A/B-, CARD11-, and MYD88 mutations. Further genomic aberrations include amplifications of BCL2 and inactivating mutations in PRMD1. These molecular insights have spurred the development of novel autochthonous mouse models that faithfully mimic the biology and genetics of human ABC-DLBCL and could serve as preclinical platforms in future experiments. Furthermore, our genomic understanding of the disease now enables us to develop and validate novel targeted therapeutic intervention strategies that aim at decapitating non-physiological NFjB activity and repressing anti-apoptotic BCL2 signaling. In this review, we highlight these recent developments and make suggestions for further tool development and the design and stratification of future clinical trials.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knittel, Gero UNSPECIFIED UNSPECIFIED UNSPECIFIED Liedgens, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Korovkina, Darya UNSPECIFIED UNSPECIFIED UNSPECIFIED Pallasch, Christian P. UNSPECIFIED orcid.org/0000-0001-5675-6905 UNSPECIFIED Reinhardt, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-254424
DOI:	10.1111/ejh.12792
Journal or Publication Title:	Eur. J. Haematol.
Volume:	97
Number:	6
Page Range:	S. 499 - 511
Date:	2016
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1600-0609
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; ONCOGENIC CARD11 MUTATIONS; TYROSINE KINASE INHIBITOR; NON-HODGKIN-LYMPHOMA; FOLLICULAR LYMPHOMA; MOLECULAR SUBTYPES; AUTOIMMUNE-DISEASE; ANTITUMOR-ACTIVITY; UBIQUITIN LIGASE; DEPENDENT KINASE Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25442