2013 - 2021
Genome-wide Mutation Discovery and Delineation of the Somatic Aberration Networks in MPN.
The project part leader, Robert Kralovics, conducted pioneering studies on JAK2 V617F+ MPN, discovered primary lesions and genetic factors in MPN. He established genome-wide screen assays for the detection of mutations and SNP in neoplastic cells. His research is dedicated to classical MPN, including JAK2 V617F-mutated variants. During the preparation for this SFB, Robert studied a large cohort of MPN patients with high-resolution SNP arrays and identified 18 major recurrent chromosomal aberrations potentially involved in disease initiation and/or progression.
The aims in project #02 were to identify relevant genes somatically mutated in ET, PV, and PMF for diagnostic and prognostic applications and to define relevant pathways involved in disease initiation and transformation. As a second step, #02 aimed to functionally evaluate gain-of-function and loss-of-function mutations in vitro and in vivo with an emphasis on the mechanism of action of mutated CALR, and finally to determine the effects of anti-CALR antibodies, pegylated interferon-alpha (IFN-A), and selective small molecule inhibitors on growth and survival of MPN stem- and progenitor cells in vitro and in vivo.