{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:32:18Z","timestamp":1791124338993,"version":"4.1.0"},"reference-count":84,"publisher":"Wiley","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA129952"],"award-info":[{"award-number":["R01 CA129952"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advances in Hematology"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>The immunomodulatory agent, lenalidomide, is a structural analogue of thalidomide approved by the US Food and Drug Administration for the treatment of myelodysplastic syndrome (MDS) and multiple myeloma (MM). This agent is also currently under active investigation for the treatment of chronic lymphocytic leukemia (CLL) and non-Hodgkin\u2019s lymphoma (NHL), as well as in drug combinations for some solid tumors and mantle cell lymphoma (MCL). Although treatment with lenalidomide has translated into a significant extension in overall survival in MM and MDS and has superior safety and efficacy relative to thalidomide, the mechanism of action as it relates to immune modulation remains elusive. Based on preclinical models and clinical trials, lenalidomide, as well as other structural thalidomide derivatives, enhances the proliferative and functional capacity of T-lymphocytes and amplifies costimulatory signaling pathways that activate effector responses and suppress inflammation. This paper summarizes our current understanding of T- and natural killer (NK) cell pathways that are modified by lenalidomide in hematopoietic neoplasms to inform future decisions about potential combination therapies.<\/jats:p>","DOI":"10.1155\/2012\/513702","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T17:02:23Z","timestamp":1343149343000},"page":"1-9","source":"Crossref","is-referenced-by-count":52,"title":["Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies"],"prefix":"10.1155","volume":"2012","author":[{"given":"Jessica M.","family":"McDaniel","sequence":"first","affiliation":[{"name":"Cancer Biology PhD Program, University of South Florida, Tampa, FL 33620, USA"},{"name":"Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pinilla-Ibarz","sequence":"additional","affiliation":[{"name":"Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"},{"name":"Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. K.","family":"Epling-Burnette","sequence":"additional","affiliation":[{"name":"Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"6","key":"1","first-page":"719","volume":"45","year":"1971","journal-title":"Bulletin of the World Health Organization"},{"issue":"6","key":"2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/j.1365-4362.1980.tb00342.x","volume":"19","year":"1980","journal-title":"International Journal of Dermatology"},{"issue":"10","key":"3","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/art.1780271006","volume":"27","year":"1984","journal-title":"Arthritis and Rheumatism"},{"issue":"5","key":"4","first-page":"487","volume":"11","year":"1993","journal-title":"Clinical and Experimental Rheumatology"},{"issue":"3","key":"5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/BF02054255","volume":"5","year":"1986","journal-title":"Clinical Rheumatology"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1021\/jm9603328"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-2-36"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1179\/102453310X12647083620921"},{"issue":"1","key":"9","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1177\/107327481201900106","volume":"19","year":"2012","journal-title":"Cancer Control"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-991"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/35074122"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.11.1885"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041668"},{"issue":"9","key":"14","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S1074-7613(94)80021-9","volume":"1","year":"1994","journal-title":"Immunity"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.1.185"},{"issue":"3","key":"16","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1084\/jem.155.3.768","volume":"155","year":"1982","journal-title":"Journal of Experimental Medicine"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021637"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1038\/nature04790"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2010.04.010"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0361"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05286.x"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2005.25.604"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.048496"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279893"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1038\/86297"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0620-4"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404869"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.359"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1221"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1080\/1042819021000029993"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1385\/MO:22:3:291"},{"key":"32"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25983"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002460"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177319"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-356063"},{"key":"37"},{"key":"38"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.3109\/10428190903350405"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.0401"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.8133"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-130120"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(06)70723-9"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1172\/JC135017"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901166106"},{"key":"46","volume":"112","year":"2008","journal-title":"Blood"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08882.x"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25748"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021650"},{"issue":"4","key":"50","first-page":"512","volume":"99","year":"1982","journal-title":"Journal of Laboratory and Clinical Medicine"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041875"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.174"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(95)00050-X"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1995.1076"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.10.2992"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.1.230"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181a95198"},{"issue":"2","key":"58","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.4049\/jimmunol.131.2.1024","volume":"131","year":"1983","journal-title":"The Journal of Immunology"},{"issue":"12","key":"59","doi-asserted-by":"crossref","first-page":"7381","DOI":"10.4049\/jimmunol.166.12.7381","volume":"166","year":"2001","journal-title":"The Journal of Immunology"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002597"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.1.210"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0512-7"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-278432"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1422"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-010-0919-9"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-360255"},{"key":"67","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.016"},{"key":"68","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090331"},{"key":"69","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-271874"},{"key":"70","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4405"},{"key":"71","doi-asserted-by":"publisher","DOI":"10.1038\/ni1582"},{"key":"72","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1091"},{"key":"73","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21468"},{"key":"74","volume":"27, 15s","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"75","volume":"114, article 2376","year":"2009","journal-title":"Blood"},{"key":"76","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.04.009"},{"key":"77","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-348656"},{"key":"78","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-225979"},{"issue":"6","key":"79","first-page":"588","volume":"10","year":"2009","journal-title":"Current Opinion in Investigational Drugs"},{"key":"80","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000303"},{"key":"83","volume":"116","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"issue":"16","key":"84","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1200\/JCO.2011.37.2649","volume":"30","year":"2012","journal-title":"Journal of Clinical Oncology"},{"key":"85","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.3.1178"},{"key":"86","doi-asserted-by":"publisher","DOI":"10.2174\/156800907780006940"}],"container-title":["Advances in Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ah\/2012\/513702.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ah\/2012\/513702.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ah\/2012\/513702.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T12:56:25Z","timestamp":1687611385000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/ah\/2012\/513702\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":84,"alternative-id":["513702","513702"],"URL":"https:\/\/doi.org\/10.1155\/2012\/513702","relation":{},"ISSN":["1687-9104","1687-9112"],"issn-type":[{"value":"1687-9104","type":"print"},{"value":"1687-9112","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012]]}}}