Project overview
The mission of this project is to create a Research Network and build a platform that contains and provides unique open-access resources and innovative tools, devoted to accelerating the generation of knowledge for fast translation and implementation into new population-based early cancer detection and prevention programs focused on MBL with CLL, other leukaemia or lymphoma phenotype.<br/><br/>General Objective<br/>The general objective of this proposal is to set up a Research Network and Platform aimed at developing and facilitating access to unique resources and innovative tools essential for the broader cancer community, and at performing research that will accelerate generation of knowledge which is a key for better understanding the role of immune dysregulation and the molecular and cellular mechanisms and pathways involved in progression and malignant transformation of MBL to overt disease. Our goal is to translate these new advances into improved early diagnosis, risk stratification and prevention of death, progression, and malignant transformation of MBL to overt disease focusing on younger adults from the general population. To accelerate validation of the potential (clinical) relevance of the results of the project across other haematological cancer types, two additional B-cell tumour models are also addressed in this proposal: the MGUS-MM and MZL-like MBL-MZL models.<br/><br/>To reach this general aim four specific objectives have been delineated:<br/><br/>Objective 1 - To create open‐access research infrastructures for early diagnosis of (mature B-cell) leukemia<br/>The aim is to create key open-access unique research infrastructures under the umbrella of an international research network on early cancer diagnosis focused on mature B-cell malignancies, that includes:<br/>a (genomics) data management platform,<br/>a biobank of plasma, purified tumour cells, normal cells and their nucleic acid sub-components (e.g. DNA, mRNA, miRNA), together with<br/>detailed bulk and single-cell genetic, epigenetic and transcriptomic maps of blood-derived clonal/tumour B cells and immune profiles of individuals with MBL and MGUS in the general population.<br/><br/>Objective 2 - To develop novel HTP diagnostic screening for MBL (+ MGUS) in the general population<br/>The aim is to develop:<br/>cost-effective,<br/>standardized and<br/>highly sensitive laboratory protocols and tools for fast high-throughput diagnostic screening of MBL plus MGUS in the general population.<br/><br/>Objective 3 - Identification of biomarkers of progression and survival and (potential) targets for early intervention<br/>The aim is to identify biomarkers of progression and survival, and (potential) targets for early intervention in MBL and MGUS subjects from the general population, to prevent both:<br/>progression and malignant transformation to CLL, MZL and MM and<br/>premature death based on the characteristics of MBL and MGUS tumour cells and their interaction with immune cells.<br/><br/>Objective 4 - To elaborate educational materials/tools, provide certified training focused on B cell malignancies<br/>The aim is to elaborate educational materials and tools, and to provide certified training programs and workshops, that will:<br/>accelerate worldwide dissemination and<br/>translation into routine practice of the results of the project, in the field of national population-based early cancer diagnostic screening, monitoring and prevention programs, focused on B-cell malignancies.
