UMRS 1349 at Sorbonne Paris Nord University

Not only are we translating our basic science into daily practice and European recommendations for disease stratification, but we are also adding economic and societal value to our knowledge on signaling targets.

1) We have developed 2 patents with INSERM Transfert/SATT IdF by determining the cytokine profiles and their functional impact on tumor microenvironment in skin and blood diseases. Our aim is to provide new clinical care solutions for patients:

a) in inflammatory skin disease with immune dysregulation (WO2017162604A1, C Le Roy, CIFRE and BIP-OSEO funding, “DDR” Start-up at Incub’13 USPN) in collaboration with Dermance.

b) on the stratification of leukemia (WO2019234221A1, C Le Roy/N Varin-Blank) with the characterization of regulatory factors involved in immune tolerance to tumor cells. We described a new stratification score based on the variable expression of regulatory factors, including IL10, TGFb1, FOXP3 and Indoleamine 2,3 dioxygenase (IDO).

2) We have translated basic knowledge into daily practice and routine disease stratification. Sequencing of the IGHV gene and 11 most frequently mutated signaling effectors (TP53, NOTCH1, ATM, POT1, RPS15, FBXW7, BIRC3, SF3B1, XPO1, IKZF3, MYD88) is now performed on most samples collected during the clinical workup of patients. Additional genetic mutations, associated with treatment resistance, are also included in routine monitoring of tumor clones or subpopulations. By collecting a large cohort of TP53-mutated CLL samples, we have identified two mutations, one of which was recurrent in patients previously treated with chlorambucil and who show resistance to kinase inhibitors with poorer outcome (G Lazarian AJH 2022; F Baran-Marszak 2020, collaboration with the FILO group). A new gene panel is being designed to detect relapse in patients after treatment.