Anaplastic large cell lymphoma (ALCL) is a rare and aggressive peripheral T-cell lymphoma
affects lymph nodes and extra-nodal sites with characteristic skin lesions. Approximatively half of the tumors express the NPM1-ALK fusion from the translocation t(2;5)(p23;q32). In the present study, the inventors identify ROR2 as progressively up regulated thought
tumorigenesis. Patient samples show a significantly high ROR2 expression (transcriptomic
data) as well as a strong ROR2 protein expression (IHC) with some tumors displaying a clear
membrane signal. ROR2 mRNA expression level is also positively correlated to NPM-ALK
expression level in tumor cells and is not expressed in normal T cells. In addition, ROR2 protein level is significantly increased in resistant cells to the ALK inhibitor, crizotinib, used in clinical trials for children with refractory tumors. This result opens the road to ROR2 specific therapies: ROR2 inhibitors, monoclonal antibodies therapies or even ROR2 specific CAR cells, including for ALCL ALK(+) resistant tumors.