{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:07:41Z","timestamp":1772752061875,"version":"3.50.1"},"reference-count":31,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,8,15]]},"abstract":"<jats:p>Rexinoids binding to both the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families of rexinoid receptors have demonstrated clinical activity in hematologic malignancies and have been shown to mediate genes associated with both growth and differentiation. RXR rexinoids have demonstrated efficacy in the treatment of cutaneous T-cell lymphomas, but the mechanism of action is unclear. We explored the immunomodulatory effects of RAR and RXR rexinoids in human T- and B-cell leukemia cells and demonstrated that RXR rexinoids are capable of up-regulating high-affinity interleukin-2 receptor (IL-2R) expression. Exposure to 10\u22126 to 10\u221210 M bexarotene or Panretin for 48 hours was associated with increased expression of both the p55 and p75 subunits of the IL-2R in T-cell leukemias and p75 in B-cell leukemias. Furthermore, rexinoid exposure enhanced susceptibility of the cells to denileukin diftitox fusion toxin-targeting and -intoxicating cells expressing high-affinity IL-2R. These results suggest a rationale for combining rexinoids with IL-2R\u2013targeted therapies in lymphoid malignancies as well as possibly in autoimmune diseases.<\/jats:p>","DOI":"10.1182\/blood-2002-01-0300","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T21:48:18Z","timestamp":1033508898000},"page":"1399-1403","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":70,"title":["Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox"],"prefix":"10.1182","volume":"100","author":[{"given":"Gullu","family":"Gorgun","sequence":"first","affiliation":[{"name":"From the Department of Hematology Oncology and Experimental Therapeutics, Tufts New England Medical Center, Boston, MA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francine","family":"Foss","sequence":"additional","affiliation":[{"name":"From the Department of Hematology Oncology and Experimental Therapeutics, Tufts New England Medical Center, Boston, MA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021221432184400_B1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/345224a0","article-title":"Nuclear receptor that identifies a novel retinoic acid response pathway.","volume":"345","author":"Mangelsdorf","year":"1990","journal-title":"Nature."},{"key":"2020021221432184400_B2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1006\/excr.2000.5113","article-title":"Retinoid X receptor alpha and retinoic acid receptor gamma mediate expression of genes encoding tight-junction proteins and barrier function in F9 cells during visceral endodermal differentiation.","volume":"263","author":"Kubota","year":"2001","journal-title":"Exp Cell Res."},{"key":"2020021221432184400_B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.bjc.6690312","article-title":"Retinoids: present role and future potential.","volume":"80","author":"Evans","year":"1999","journal-title":"Br J Cancer."},{"key":"2020021221432184400_B4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1172\/JCI1581","article-title":"Retinoids increase human apo C-III expression at the transcriptional level via the retinoid X receptor. 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fungoides.","volume":"39","author":"Saleh","year":"1998","journal-title":"J Am Acad Dermatol."},{"key":"2020021221432184400_B10","first-page":"399","article-title":"Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2.","volume":"91","author":"LeMaistre","year":"1998","journal-title":"Blood."},{"key":"2020021221432184400_B11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/jcb.240630503","article-title":"T-cell lymphoma cell lines (HUT102 and HUT78) established at the National Cancer Institute: history and importance to understanding the biology, clinical features, and therapy of cutaneous T-cell lymphomas (CTCL) and adult T-cell leukemia-lymphomas (ATLL).","volume":"24","author":"Bunn","year":"1996","journal-title":"J Cell Biochem Suppl."},{"key":"2020021221432184400_B12","doi-asserted-by":"crossref","first-page":"9485","DOI":"10.1073\/pnas.86.23.9485","article-title":"Sequential effects of interleukin 2-diphtheria 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Immunol."},{"key":"2020021221432184400_B16","first-page":"2889","article-title":"All-trans-retinoic acid modulates expression levels of thyroglobulin and cytokines in a new human poorly differentiated papillary thyroid carcinoma cell line, KTC-1.","volume":"85","author":"Kurebayashi","year":"2000","journal-title":"J Clin Endocrinol Metab."},{"key":"2020021221432184400_B17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/(SICI)1097-4652(199804)175:1<68::AID-JCP8>3.0.CO;2-A","article-title":"RAR-, not RXR, ligands inhibit cell activation and prevent apoptosis in B-lymphocytes.","volume":"175","author":"Lomo","year":"1998","journal-title":"J Cell Physiol."},{"key":"2020021221432184400_B18","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/311626a0","article-title":"Molecular cloning and expression of cDNAs for the human interleukin-2 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that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex.","volume":"83","author":"Tsudo","year":"1986","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021221432184400_B26","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1093\/nar\/18.13.3697","article-title":"The human interleukin-2 receptor beta-chain gene: genomic organization, promoter analysis and chromosomal assignment.","volume":"18","author":"Shibuya","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"2020021221432184400_B27","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1084\/jem.167.2.612","article-title":"Interleukin 2 receptor-targeted cytotoxicity: interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein.","volume":"167","author":"Bacha","year":"1988","journal-title":"J Exp Med."},{"key":"2020021221432184400_B28","first-page":"27","article-title":"Distribution of lymphocytes with interleukin-2 receptors 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