| Title | Clinical and in vitro resistance to bexarotene in adult T cell leukemia: loss of RXR-alpha receptor. | | Author(s) | Lin JH, Kim EJ, Bansal A, Seykora J, Richardson SK, Cha XY, Zafar S, Nasta S, Wysocka M, Benoit B, Rook AH, Fakharzadeh SS | | Institution | Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States. | | Source | Blood 2008 Jun 16. | | Abstract | The oral rexinoid, bexarotene (Targretin), is widely used for treatment of cutaneous T-cell lymphomas (CTCL). We recently reported the first case of adult T-cell Leukemia/Lymphoma (ATLL) that rapidly responded to combination therapy of bexarotene and interferon (IFN)-alpha2b with complete clinical response.(1) We demonstrated that bexarotene induced apoptosis of the patient's malignant peripheral blood T-cells in vitro. However, our patient developed skin and nodal relapse 180 days after starting treatment. We now demonstrate that his peripheral blood malignant T-cells became resistant to bexarotene-induced apoptosis. We investigated potential mechanisms that may cause aberrations in the RXR receptor subunits, RXR-alpha and RXR-beta, to account for these findings. Sequence analysis did not reveal acquisition of mutations in the genes encoding RXR-alpha and RXR-beta by resistant cells. We assessed RXR-alpha and RXR-betaexpression by Western blot analysis and found that resistant cells had significantly decreased RXR-alpha expression compared to pre-therapy bexarotene-sensitive cells. Our findings indicate that reduced expression of the RXR-alpha receptor subunit may represent a mechanism for resistance to bexarotene in T-cell malignancies. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18559673 |
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