2013 - 2021

Identification of molecular targets in neoplastic stem cells (SC) and the SC niche in CML and other MPN.

The project part leader, Peter Valent is an expert in the field of MPN and will serve as the Speaker and Coordinator of this SFB. The group has long-lasting experience and great expertise in experimental and translational hematology. With this group, the speaker has developed several new concepts in the field of MPN in the past few years, developed several biomarkers, prognostic factors and scores, and established new treatment concepts. During the past 10 years, his group focused on SM/MCL and CML, and more recently also on eosinophil disorders. Another focus in this research are neoplastic/leukemic SC. The speaker coordinates a national CML platform, a European Competence Network on Mastocytosis, and an International Working Group on Eosinophil Disorders. He is Scientific Director of the Ludwig-Boltzmann Cluster Oncology (topic: neoplastic SC) at the Medical University of Vienna, and co-chairs a Working Group for neoplastic SC in the European Hematology Association (EHA).

The primary aim in his project in the current SFB is to evaluate the diagnostic and prognostic potential of new LSC markers and to validate novel LSC targets in Ph+ CML, JAK2- or CALR-mutated classical MPN, and other MPN. Other aims will involve investigating the expression and function of drug targets in BM endothelial cells and osteoblastic cells, exploring the effects of targeted drugs on LSC and LSC-niche interactions, and the identification of drugs and drug combinations that can overcome multiple forms of drug resistance (molecular, niche-induced, immune-mediated) in LSC in CML and other MPN.

Project #04 contributes substantially to the common goal of this SFB for several reasons: Project #04 is an integral component of the cooperative F47-network for several reasons: first, the PI runs a clinical center of excellence for MPN including rare entities, and coordinates the collection, storage, and distribution of freshly obtained primary patient-derived cells and follow up samples in various MPN cohorts together with the biobank-team. In addition, #04 provides all clinically relevant parameters, follow up information, and clinical endpoints (OS and PFS) required in various SFB collaborations (#06, #07, #10, #11). Second, based on data accumulated in the first period, the team of #04 is able to provide protocols for LSC analysis, enrichment, and culture, as well as purified (sorted) LSC (CML or other MPN, as intact cells or DNA/RNA) to the consortium. The purification of more mature neoplastic cells (per lineage) by flow cytometry is also standard in the lab of the PI. The group has also established several cell line models relevant to the current SFB, including LSC-like and pluripotent (iPSC-like) cell lines generated from MPN patients. Finally, the group has vast experience in BM histopathology and immunohistochemistry in human MPN. All these facilities and tools, including primary LSC and clinical data sets will be shared in this SFB.