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In this incurable and recurring pathology, the interval between relapses tends to decrease while aggressiveness increases, sometimes resulting in the transformation to higher\u2010grade lymphoma. These evolutions are particularly difficult to anticipate, resulting from complex clonal evolutions where multiple subclones compete and thrive due to their capacity to proliferate and resist therapies. Here, to apprehend further these processes, we used a high\u2010throughput RNA sequencing approach to address simultaneously the B\u2010cell immunoglobulin repertoires and T\u2010cell immunoglobulin repertoires repertoires of lymphoma cells and their lymphoid microenvironment in a large cohort of 131 FL1\/2\u20103A patients. Our data confirm the existence of a high degree of intra\u2010clonal heterogeneity in this pathology, resulting from ongoing somatic hyper\u2010mutation and class switch recombination. Through the evaluation of the Simpson ecological\u2010diversity index, we show that the contribution of the cancerous cells increases during the course of the disease to the detriment of the reactive compartment, a phenomenon accompanied by a concomitant decrease in the diversity of the tumoral population. Clonal evolution in FL thus contrasts with many tumors, where clonal heterogeneity steadily increases over time and participates in treatment evasion. In this pathology, the selection of lymphoma subclones with proliferative advantages progressively outweighs clonal diversification, ultimately leading in extreme cases to transformation to high\u2010grade lymphoma resulting from the rapid emergence of homogeneous subpopulations.<\/jats:p>","DOI":"10.1002\/hem3.50","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T13:15:54Z","timestamp":1708953354000},"source":"Crossref","is-referenced-by-count":1,"title":["Analysis of immunoglobulin\/T\u2010cell receptor repertoires by high\u2010throughput RNA sequencing reveals a continuous dynamic of positive clonal selection in follicular lymphoma"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-4542","authenticated-orcid":false,"given":"Victor","family":"Bob\u00e9e","sequence":"first","affiliation":[{"name":"INSERM U1245, Centre Henri Becquerel, UNIROUEN University of Normandie  Rouen France"},{"name":"Department of 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