Understanding the pathogenesis of chronic lymphocytic leukemia to develop novel targeted therapies
Dr. Martina Seiffert
Chronic lymphocytic leukemia
B cell chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the Western World. It is characterized by the expansion of mature B lymphocytes and shows a heterogeneous clinical course, which can be partly explained by specific genomic aberrations or B cell receptor characteristics. Recent therapeutic advances have led to very good initial response rates. However, a large proportion of patients eventually relapse, and CLL remains an incurable disease. Despite extensive efforts, the underlying pathomechanism of CLL is still largely unknown and genotype specific and targeted therapies are not available. Therefore, the goal of our ongoing research activities is to establish a better understanding of the pathomechanism of CLL and to translate these findings into novel and targeted therapeutic approaches.
Overview of projects:
Identification of CLL-relevant microenvironmental factors as potential targets for novel therapies
The role of extracellular vesicles in CLL pathogenesis
High-throughput screen for novel apoptosis-inducing substances for CLL
Mouse models for CLL
Genome-wide analysis of microRNAs and their targets in CLL
Next generation sequencing to identify novel genomic aberrations with relevance in CLL development and progression
- Seiffert M, Schulz A, Ohl S, Döhner H, Stilgenbauer S, Lichter P. Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro, and present at abnormally high levels in vivo. Blood, 116: 4223-4230, 2010.
- Kovaleva V, Mora R, Park YJ, Plass C, Chiramel AI, Bartenschlager R, Döhner H, Stilgenbauer S, Pscherer A, Lichter P, Seiffert M. miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells. Cancer Res, 72: 1763-1772, 2012.
- Schulz A, Dürr C, Zenz T, Stilgenbauer S, Lichter P, Seiffert M. Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary co-cultures by altering the myeloid microenvironment. Blood, 121: 2503-2511, 2013.
- Meier J, Hovestadt V, Zapatka M, Pscherer A, Lichter P, Seiffert M. Genome-wide identification of translationally inhibited and degraded miR-155 targets using RNA-interacting protein-IP. RNA Biol, 10: 1018-1030, 2013.