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Reversal of T-cell Tolerance in Myelodysplastic Syndrome through Lenalidomide Immune Modulation

Authors
Journal
Leukemia
0887-6924
Publisher
Nature Publishing Group
Publication Date
Volume
26
Issue
6
Identifiers
DOI: 10.1038/leu.2011.359
Keywords
  • Article
Disciplines
  • Biology
  • Medicine

Abstract

Reversal of T-cell Tolerance in Myelodysplastic Syndrome through Lenalidomide Immune Modulation Jessica M. McDaniel, BS1,2, JianXiang Zou, MD2, William Fulp, PhD3, Dung-Tsa Chen, PhD3, Alan F. List, MD4, and PK Epling-Burnette, PharmD, PhD2,5 1Cancer Biology PhD Program, University of South Florida, Tampa, FL 33612 2Department of Immunology, Tampa, FL 33612 3Biostatistics Department, Tampa, FL 33612 4Department of Malignant Hematology at H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612 Letter to the Editor Myelodysplastic syndromes (MDS) represent a spectrum of senescence-dependent, hematopoietic stem cell disorders1 with dysplastic cytological features, ineffective hematopoiesis, and a propensity for transformation into acute myeloid leukemia (AML)2. Response biomarkers to inform delegation of FDA-approved therapies such as the thalidomide analog lenalidomide (Revlimid ®, Celgene Inc.), are needed to improve outcomes. High rates of erythroid response to lenalidomide occur in del(5q)-MDS patients due to suppression of haplodeficient phosphatases encoded within the proximal Commonly Deleted Region (CDR)3. A previous report showing that bone marrow lymphoid aggregates appear in association with hematologic response implicates immune modulation in this process4. Thalidomide, lenalidomide, and other structural analogues of this drug class induce potent immune modulation independent of del(5q), with documented activation of T- cells and NK-cells both in vitro and in vivo in multiple myeloma and chronic lymphocytic leukemia5-7. In an effort to understand how lenalidomide’s immunomodulatory activity may be linked to hematologic response in MDS, we evaluated T-cell activity before and after lenalidomide treatment in vitro, and examined in vivo immune correlates related to hematologic response based on International Working Group (IWG) 2000 criteria. For this analysis, one hundred patients with pathologically defined MDS were consented at Moffitt Cancer Center to evaluate im

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