Universität zu Köln

Frenzel, Lukas P., Reinhardt, H. Christian and Pallasch, Christian P. ORCID: 0000-0001-5675-6905 (2016). Concepts of Chronic Lymphocytic Leukemia Pathogenesis: DNA Damage Response and Tumor Microenvironment. Oncol. Res. Treat., 39 (1-2). S. 9 - 16. BASEL: KARGER. ISSN 2296-5262

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Abstract

Pathogenesis of chronic lymphocytic leukemia (CLL) is characterized by specific genetic aberrations and alterations of cellular signaling pathways. In particular, a disturbed DNA damage response (DDR) and an activated B-cell receptor signaling pathway play a major role in promoting CLL cell survival. External stimuli are similarly essential for CLL cell survival and lead to activation of the PI3K/AKT and MAPK pathways. Activation of nuclear factor-kappa B (NFkB) influences the disturbed antiapoptotic balance of CLL cells. Losses or disabling mutations in TP53 and ATM are frequent events in chemotherapy- naive patients and are further enriched in chemotherapy- resistant patients. As these lesions define key regulatory elements of the DDR pathway, they also determine treatment response to genotoxic therapy. Novel therapeutic strategies therefore try to circumvent defective DDR signaling and to suppress the pro-survival stimuli received from the tumor microenvironment. With increasing knowledge on specific genetic alterations of CLL, we may be able to target CLL cells more efficiently even in the situation of mutated DDR pathways or protection by microenvironmental stimuli. (C) 2016 S. Karger GmbH, Freiburg

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Frenzel, Lukas P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, H. Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Pallasch, Christian P. UNSPECIFIED orcid.org/0000-0001-5675-6905 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-291232
DOI:	10.1159/000443820
Journal or Publication Title:	Oncol. Res. Treat.
Volume:	39
Number:	1-2
Page Range:	S. 9 - 16
Date:	2016
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	2296-5262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language B-CELL-RECEPTOR; NF-KAPPA-B; IDENTIFIES RECURRENT MUTATIONS; TOLL-LIKE RECEPTORS; TYROSINE KINASE; BIOLOGICAL DIVERSITY; GENOMIC ABERRATIONS; THERAPEUTIC TARGET; OBLIMERSEN SODIUM; GENE-EXPRESSION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29123