IL-2/IL-2R signaling and IL-2Rα-targeted therapy in anaplastic large cell lymphoma.

Pathologie (Heidelb)

Human Oncology & Pathogenesis Program (HOPP), Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.

Published: August 2022

Anaplastic large cell lymphoma (ALCL) is a CD30-positive non-Hodgkin's T‑cell lymphoma. Despite the implementation of CD30 antibody-drug conjugate-targeted therapy into front-line treatment regimens, the prognosis of some subtypes of the disease remains unsatisfactory. In the relapsed/refractory setting, effective second-line treatment options are still lacking. However, it has been reported that blockade of direct downstream targets of activator protein‑1 (AP-1) transcription factors, which are highly dysregulated in ALCL, results in complete and sustained remission in late-stage relapsed/refractory anaplastic lymphoma kinase (ALK)-positive ALCL patients. Moreover, it has been identified that involvement of the BATF3/AP‑1 module promotes lymphomagenesis via oncogenic BATF3/IL-2/IL-2R signaling through hyperphosphorylation of ERK1/2, STAT1, and STAT5 in ALCL cells regardless of their ALK status. Therefore, targeting BATF3/IL-2/IL-2R signaling may represent a novel therapeutic alternative for ALCL patients.

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http://dx.doi.org/10.1007/s00292-022-01108-xDOI Listing

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