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Integrated next-generation flow cytometry and sequencing to uncover the pathway of curability in multiple myeloma

Periodic Reporting for period 3 - MYELOMANEXT (Integrated next-generation flow cytometry and sequencing to uncover the pathway of curability in multiple myeloma)

Reporting period: 2019-09-01 to 2021-02-28

According to the European Network of Cancer Registries, around 60,000 people are living with Multiple myeloma (MM) in Europe and there are 21,420 new cases and 15,000 deaths every year. Continuous treatment of MM has become one of the most expensive among haematological malignancies and it fails to cure most patients with this disease. In this project, we aim to help drawing the pathway of curing MM by addressing critical questions that remain unanswered: “Are there MM cancer stem cells?”, “Why does a quiescent clone become aggressive in some patients while remains stable in others?”, “What are the mechanisms responsible for primary and acquired chemoresistance?”, and “What drives disease dissemination?”. The successful execution of this project is expected to provide a framework of data and research models to accelerate curing MM. Due to the similarity between this disease and some hematological malignancies and even solid tumors, the deliverables of this project could be of major long-term benefit to the society.
The amount of work performed can be measured, for example, by the number of original manuscripts published during the past 2.5 years: 12. Of note, these manuscripts were published in top Journals of the field (eg. Nat Med, Blood, Leukemia) and had high impact in the scientific community with a total of 142 non-self-citations. During this period, the results obtained in this project were presented in a total of 6 oral communications in the prestigious American Society of Hematology (ASH) and European Hematology Association (EHA) meetings. Such dissemination was made alongside the execution of other specific aims of the project; thus, we envision more scientific production in the upcoming years and, most importantly, of significant contribution to the society. Among the results achieved so far, it could be highlighted the first-ever genetic characterization of circulating tumor cells and minimal residual disease clones, as well as the first-ever integration of minimal residual disease and immune monitoring to predict patients’ outcome. These achievements advanced our knowledge of the disease, and fostered many scientific groups around the world to investigate in these research areas.
The advent of novel single-cell technologies has been progressively incorporated to execute some objectives of the project. This will increase the quality of data generated in this project and is of paramount importance to deliver, for example, a detailed characterization of patients’ immune cells. In accordance to the successful execution of the project during this period, we expect the following results at the end project: i) the signature of circulating tumor cells and ultra-chemoresistant minimal residual disease cells, ii) the hierarchical place of putative cancer stem cells, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures.