Survival Signals and Targets for Therapy in Breast Implant-Associated ALK- Anaplastic Large Cell Lymphoma
Cette étude analyse les caractéristiques de lignées cellulaires établies à partir d'échantillons prélevés sur des patientes ayant développé une forme de lymphome non hodgkinien associé à la rupture d'un implant mammaire
Purpose: Anaplastic lymphoma kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin's lymphoma (T-ALCL) in patients with textured saline and silicone breast implants is a recently recognized clinical entity for which etiology and optimal treatment remain unknown. Experimental design: Using three newly established model cell lines from patient biopsy specimens, designated T-cell BReast Lymphoma (TLBR) -1 to -3, we characterized the phenotype and function of these tumors to identify mechanisms of cell survival and potential therapeutic targets. Results: Cytogenetics revealed chromosomal atypia with partial or complete trisomy and absence of the NPM-ALK (2;5) translocation. Phenotypic characterization showed strong positivity for CD30, CD71, T-cell CD2/5/7, and antigen presentation (HLA-DR, CD80, CD86) markers, and interleukin (IL)-2 (CD25, CD122) and IL-6 receptors. Studies of these model cell lines demonstrated strong activation of STAT3 signaling, likely related to autocrine production of IL-6 and decreased SHP-1. STAT3 inhibition, directly or by recovery of SHP-1, and CHOP chemotherapy reagents, effectively kill cells of all three TLBR models in vitro and may be pursued as therapies for patients with breast implant-associated T-ALCL. Conclusions: The TLBR cell lines closely resemble the primary breast implant-associated lymphomas from which they were derived, and as such provide valuable preclinical models to study their unique biology.