Universität zu Köln

Knittel, Gero, Rehkaemper, Tim, Nieper, Pascal, Schmitt, Anna, Fluemann, Ruth and Reinhardt, H. Christian (2018). DNA damage pathways and B-cell lymphomagenesis. Curr. Opin. Hematol., 25 (4). S. 315 - 323. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1531-7048

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Abstract

Purpose of review Recent lymphoma genome sequencing projects have shed light on the genomic landscape of indolent and aggressive lymphomas, as well as some of the molecular mechanisms underlying recurrent mutations and translocations in these entities. Here, we review these recent genomic discoveries, focusing on acquired DNA repair defects in lymphoma. In addition, we highlight recently identified actionable molecular vulnerabilities associated with recurrent mutations in chronic lymphocytic leukemia (CLL), which serves as a model entity. Recent findings The results of several large lymphoma genome sequencing projects have recently been reported, including CLL, T-PLL and DLBCL. We align these discoveries with proposed mechanisms of mutation acquisition in B-cell lymphomas. Moreover, novel autochthonous mouse models of CLL have recently been generated and we discuss how these models serve as preclinical tools to drive the development of novel targeted therapeutic interventions. Lastly, we highlight the results of early clinical data on novel compounds targeting defects in the DNA damage response of CLL with a particular focus on deleterious ATM mutations. Summary Defects in DNA repair pathways are selected events in cancer, including lymphomas. Specifically, ATM deficiency is associated with PARP1- and DNA-PKcs inhibitor sensitivity in vitro and in vivo.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knittel, Gero UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehkaemper, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Nieper, Pascal UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Fluemann, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, H. Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-181226
DOI:	10.1097/MOH.0000000000000433
Journal or Publication Title:	Curr. Opin. Hematol.
Volume:	25
Number:	4
Page Range:	S. 315 - 323
Date:	2018
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1531-7048
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; CLASS-SWITCH RECOMBINATION; STRAND BREAK REPAIR; IMMUNOGLOBULIN VARIABLE GENES; ONCOGENE-INDUCED SENESCENCE; INDUCED CYTIDINE DEAMINASE; 5 NONCODING REGION; SOMATIC HYPERMUTATION; POLYMERASE-ETA; CHROMOSOMAL TRANSLOCATIONS Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18122