earlyRTdx · A single-cell-based solution for an early diagnosis of Richter transformation in patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in Western countries with an incidence of ~4.6 newly diagnosed cases per 100,000 people per year. Among them, 5-10% of patients with CLL develop Richter transformation (RT), an aggressive transformation of CLL into a high-grade lymphoma, conferring poor outcome. RT is currently the principal unmet medical need in patients with CLL. Thanks to recent findings by our group, we know that there is a time window for early detection of RT years to decades before it is currently diagnosed using available pathological techniques as a full-blown tumor, often disseminated throughout the body. An early detection of RT may allow the design of early intervention schemes aiming to treat and eliminate RT at an early, probably indolent and clinically inoffensive, stage. The aim of this project is to design, test, and validate a novel single-cell-based solution, named earlyRTdx, capable of detecting the seeds of RT before their final expansion and clinical manifestation. To that aim, we will (1) select the genomic, transcriptomic, and epigenetic (DNA methylation) features that distinguish RT and CLL cells, (2) ensemble the joint analysis of these different molecular features into a unique, single-cell-based assay, which will be validated by screening both previously studied and new CLL/RT samples from different hospitals as well as by assessing its performance within a real diagnostic environment, and (3) conduct innovation activities to protect the intellectual property generated and license the solution. Altogether, the earlyRTdx shall represent the first-in-class in vitro diagnostics solution for early RT detection. This solution will provide a timely diagnosis of RT, which is the first step towards aiming to eradicate the seeds of this aggressive – lethal in most situations – evolution of CLL.