Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia
| Autor: | August Stuart, Zainul Hasanali, Elliot M. Epner, Violetta V. Leshchenko, Samir Parekh, Bikramajit Singh Saroya, Sara Shimko, Mithun Vinod Shah, Kamal Sharma, Thomas P. Loughran, Juanita J. Evans |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology medicine.medical_specialty Immunoconjugates medicine.drug_class medicine.medical_treatment Ki-1 Antigen Biology Antibodies Monoclonal Humanized Real-Time Polymerase Chain Reaction Epigenesis Genetic Leukocyte Count Internal medicine Antineoplastic Combined Chemotherapy Protocols STAT5 Transcription Factor medicine Humans RNA Messenger Promoter Regions Genetic Brentuximab vedotin Cladribine Alemtuzumab Aged Cell Proliferation Oligonucleotide Array Sequence Analysis Skin Brentuximab Vedotin Gene Expression Regulation Leukemic Histone deacetylase inhibitor General Medicine Immunotherapy Middle Aged medicine.disease Chromatin Treatment Outcome Drug Resistance Neoplasm Leukemia Prolymphocytic T-Cell Immunology Monoclonal Commentary T-cell prolymphocytic leukemia Female Epigenetic therapy medicine.drug |
| Zdroj: | Science Translational Medicine. 7 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | T cell prolymphocytic leukemia (T-PLL) is a rare, mature T cell neoplasm with distinct features and an aggressive clinical course. Early relapse and short overall survival are commonplace. Use of the monoclonal anti-CD52 antibody alemtuzumab has improved the rate of complete remission and duration of response to more than 50% and between 6 and 12 months, respectively. Despite this advance, without an allogeneic transplant, resistant relapse is inevitable. We report seven complete and one partial remission in eight patients receiving alemtuzumab and cladribine with or without a histone deacetylase inhibitor. These data show that administration of epigenetic agents can overcome alemtuzumab resistance. We also report epigenetically induced expression of the surface receptor protein CD30 in T-PLL. Subsequent treatment with the anti-CD30 antibody-drug conjugate brentuximab vedotin overcame organ-specific (skin) resistance to alemtuzumab. Our findings demonstrate activity of combination epigenetic and immunotherapy in the incurable illness T-PLL, particularly in the setting of previous alemtuzumab therapy. |
| Databáze: | OpenAIRE |
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