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Clin Cancer Res. 2012 Sep 1;18(17):4549-59. doi: 10.1158/1078-0432.CCR-12-0101. Epub 2012 Jul 12.

Survival signals and targets for therapy in breast implant-associated ALK--anaplastic large cell lymphoma.

Author information

1
Departments of Pathology, Medicine, and Plastic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA90033, USA.

Abstract

PURPOSE:

Anaplastic lymphoma kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphoma (T-ALCL) in patients with textured saline and silicone breast implants is a recently recognized clinical entity for which the 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 showed 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 cyclophosphamide-Adriamycin-vincristine-prednisone (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-ALCLs.

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.

PMID:
22791880
DOI:
10.1158/1078-0432.CCR-12-0101
[Indexed for MEDLINE]
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