Contact

 

Prof. Dr. med. Alwin Krämer
Phone: +49 6221 421440

E-mail: a.kraemer@dkfz.de

Unraveling the nature...

 

of chromosomal instability.

Clinical Cooperation Unit Molecular Hematology/Oncology

DKFZ
 
 
 

Our group/department has:

  • Shown that clonal heterogeneity as extracted from routine cytogenetics predicts poor prognosis in AML, which highlights the pathogenetic role of chromosomal instability in AML (Bochtler et al. J Clin Oncol 2013).

  • Mechanistically dissected cellular mechanisms underlying chromosomal instability of malignant cells, including mitotic aberrations based on centrosome amplification. We characterized these mechanisms using live observation of malignant cells (Löffler et al. Oncogene 2013), and have identified important regulators and associated pathways underlying these phenomena (Vulprecht et al. J Cell Sci 2912).

  • Used centrosomal clustering, a cancer-specific cellular defect, to develop drugs specifically targeting malignant cells (Leber et al. Sci Transl Med 2010). The most promising of the newly discovered substances, GF-15, has been characterized in vitro and in vivo, prolonged survival in a xenograft mouse model (Raab et al. Cancer Res 2012) and is currently being developed for clinical use.

2010 – 2013

  • Bochtler T, Stölzel F, Heilig CE, Kunz C, Mohr B, Jauch A, Janssen JW, Kramer M, Benner A, Bornhäuser M, Ho AD, Ehninger G, Schaich M, Krämer A. Clonal heterogeneity as detected by metaphase karyotyping is an indicator of poor prognosis in acute myeloid leukemia. J Clin Oncol. 2013 Nov 1;31(31):3898-905.

  • Löffler H, Fechter A, Liu FY, Poppelreuther S, Krämer A. DNA damage-induced centrosome amplification occurs via excessive formation of centriolar satellites. Oncogene. 2013 Jun 13;32(24):2963-72.

  • Vulprecht J, David A, Tibelius A, Castiel A, Konotop G, Liu F, Bestvater F, Raab MS, Zentgraf H, Izraeli S, Krämer A. STIL is required for centriole duplication in human cells. J Cell Sci. 2012 Mar 1;125(Pt 5):1353-62.

  • Raab MS, Breitkreutz I, Anderhub S, Rønnest MH, Leber B, Larsen TO, Weiz L, Konotop G, Hayden PJ, Podar K, Fruehauf J, Nissen F, Mier W, Haberkorn U, Ho AD, Goldschmidt H, Anderson KC, Clausen MH, Krämer A. GF-15, a novel inhibitor of centrosomal clustering, suppresses tumor cell growth in vitro and in vivo. Cancer Res. 2012 Oct 15;72(20):5374-85.

  • Leber B, Maier B, Fuchs F, Chi J, Riffel P, Anderhub S, Wagner L, Ho AD, Salisbury JL, Boutros M, Krämer A: Proteins required for centrosome clustering in cancer cells. Science Translational Medicine 26: 33ra38, 2010.