2013 - 2021

Identification of Cell-Cycle-Related Targets in BCR/ABL-Driven Neoplasms.

The project part leader, Veronika Sexl, is a well-known expert in the field of hematology and cancer research. Her area of expertise are various mouse models examining the evolution and drug resistance of Ph+ CML and Ph+ ALL.In addition, she established a model useful for the expansion of long-term in vivo repopulating murine leukemic SC in her lab. Veronika is head of the Institute of Pharmacology at the University of Veterinary Medicine Vienna (Vienna, Austria). She runs a highly active research group focusing on signal transduction pathways and drug resistance in hematopoietic neoplasms in her institute. In the current project, her group will focus on Ph+ CML and various key cell cycle regulators such as CDK6.

The aims of project #06 are to study the impact of cdk6 on disease initiation and maintenance in Jak2V617F+  and Calrdel52+ MPN mouse models, to determine CDK6-dependent genes in MPN-initiating HSPC and LSC on a genome-wide level and to study CDK6 as a potential therapeutic target in primary cells of patients suffering from various MPN, including patients with del7q.

Project #06 contributes substantially to the common goal of this SFB for several reasons: Based on our expertise in establishing mouse models using transgenic mice at the Vetmeduni Vienna, project #06 is in the pole position to support SFB members interested in mouse experiments. The Institute of Pharmacology and Toxicology runs a mouse facility under FELASA conditions that allows breeding and hosting immune-compromised mice including NSG mice that are required for human xenotransplants. The lab is well experienced in in vivo characterization of murine HSPC and LSC and shares expertise in multi-color flow cytometric analysis and sorting as well as culturing of murine LSC. The group also provides a method to expand murine leukemic stem cells in culture for weeks without loss of the ability to induce CML in mice which will be required within the SFB. These facilities will by shared to our SFB partners (#02 through #11) in the second funding period. Specific collaborations are planned with #02 (role of cdk6 in calr-mutated mice), #04 (expression and function of CDK6 in CML- and PMF LSC), #06 (STAT-CDK6 interactions), #09 (functional characterization of CDK6 in BCR-ABL1+ leukemias), and #10 (CDK6 as novel target in secondary AML).