Research

NOBIL - Novel Biomarkers in Leukemia

Code:

NC-0004

Range:

01. May 2018 - 30. April 2020

Range:

0,22 FTE

Leader:

Irena Mlinarič Raščan

Field:

3.04 Medical Sciences/Oncology

Abstract:

The project NOBIL will therefore focus on the translational research in oncology to contribute to the discovery of novel biomarkers and innovative individualized therapeutic approaches to overcome the resistance of leukemia. The proposed project emerged from ongoing effort of academics and clinicians at Faculty of pharmacy (prof. Mlinarič-Raščan) and Institute of cellular and molecular radiobiology (iRCM), CEA (Dr. Gidrol and Dr. Delić) to find an efficient and safe therapy for B cell malignancies. Our previous collaborations have successfully led to the identification of the molecules responsible for B-lymphocyte antigen receptor triggered apoptosis (Murn, 2008). The most prominent of newly identified genes was Ptger4, coding for prostaglandin EP4 receptor, which induces apoptosis in malignant B cells (Murn, 2009; Prijatelj, 2011; 2012; Gobec, 2014, Markovič, 2017). Dr. Delić´s laboratory (CEA) has identified a new form of phospho-Ku70 associated with resistance to apoptosis in chronic lymphcyitc leukemia (CLL) cells (Bouley, 2015, Grall, 2015). Moreover, we identified immunoproteasome as a potential biomarker and druggable target for the treatment of B cell malignancies. CLL is the most common hematological malignancy diagnosed in adults and is currently incurable disease associated with a high incidence of mortality. Thus, a significant unmet need remins for the treatment of relapsed and refractory CLL, which will be addressed in the proposed project focusing on: • establishment of novel clinically relevant CLL in vitro models; • the validation of biomarkers Ku70 and immunoproteasome for clinical use; • identification of safe and effective molecules for the treatment of resistant CLL via drug repurpoing and the design and evaluation of innovative therapeutic approaches to overcome the resistance of CLL. The proposed joint project is therefore highly relevant to objectives of this call, addressing the search of novel biomarkers and safe and effective therapeutic options to overcome the resistance of malignant B cells to apoptosis. The successful implementation and completion of the project are guaranteed by the expertise and experience of international and interdisciplinary teams led by prof. Irena Mlinarič-Raščan (University of Ljubljana) and dr. Jozo Delić (CEA, France). The project aims are focused on selected areas of leukemia treatment covered by partners´ expertise, experience and infrastructure and the feasibility of the project is assured by the complementarity of the partners. Our previous cooperations have resulted in successfully finished interdisciplinary studies and have led to joint proposals to EU research and innovation calls (H2020, 2015). We believe that the proposed project NOBIL will enhance the scientific cooperation, mobility of researchers and exchange of knowledge between the University of Ljubljana, Slovenia and CEA, France, which will, in turn, lead to new collaborations and joint research projects.