Andreas Agathangelidis

I began my scientific career at the Laboratory of Molecular Biology at the Hematology Clinic of the G. Papanicolaou Hospital in Thessaloniki, Greece, where I performed research in the context of my diploma thesis concerning the analysis of intraclonal diversity in patients with CLL. No or low levels of intraclonal diversity were identified overall, yet, a subset of CLL expressing IgG-switched, mutated IGHV4-34 rearrangements showed extensive intraclonal diversity implying interactions with and selection by antigen not only at the level of CLL progenitors but even after the transforming event.

During my PhD, I engaged in various studies on the immunogenetics of B-cell malignancies, mainly CLL and mantle cell lymphoma (MCL), focusing on the role of antigens in disease pathogenesis. My first main study on IG stereotypy in a series of 7424 CLL patients, the largest by far to this day, refined the molecular classification of CLL and indicated new possibilities for research on the major stereotyped subsets. My other main study concerned the in-depth immunogenetic characterization of MCL in a series of 807 patients, again the largest series worldwide. That study provided strong evidence for antigen involvement in MCL ontogeny, challenging the then prevailing view; strong support to this notion was provided by subsequent developments, most notably the remarkable clinical efficacy of signaling inhibitors in MCL. Throughout the same period, I also engaged in several other immunoprofiling studies in B-malignancies, extending from partial IGHD-IGHJ gene rearrangements in CLL and the molecular subtyping of MCL based on the integration of immunogenetics, oncogenetics and immunophenotype.

After my PhD, I joined the group of Professor Paolo Ghia for postdoc research focusing on the genetic background of MBL and CLL. Within the context of this project I gained sufficient expertise in a series of methodologies, such as flow-cytometry, cell sorting of small B cell populations as well as state-of-the-art NGS techniques i.e. whole genome sequencing and targeted deep-sequencing (manuscript under consideration). During my post-doc studies in Milan, I continued to participate in many large, multi-institutional studies on CLL covering different aspects of the pathophysiology of this disease, from genetic drivers to immune signaling. In the last 2 years, I joined the Institute of Applied Biosciences where I focus on the immunogenetics of B cell malignancies and pre-leukemic conditions using novel, state-of-the-art NGS protocols and technologies.