Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts
| Autor: | T. Andrew Lister, Alan G. Ramsay, Richard Mitter, Faridah Miraki-Moud, Abigail M. Lee, Rewas Fatah, John G. Gribben, David Taussig, Rifca Le Dieu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
CD36 Antigens Male medicine.medical_specialty Myeloid Adolescent CD3 Complex Genotype Immunological Synapses CD3 Chronic lymphocytic leukemia T-Lymphocytes Immunology Biochemistry Immune system Internal medicine hemic and lymphatic diseases medicine Humans Lymphocyte Count Aged Aged 80 and over Hematology Myeloid Neoplasia biology Gene Expression Regulation Leukemic Gene Expression Profiling Myeloid leukemia Cell Biology Middle Aged medicine.disease Leukemia Leukemia Myeloid Acute medicine.anatomical_structure biology.protein Blast Crisis |
| Zdroj: | Blood. 114(18) |
| ISSN: | 1528-0020 |
| Popis: | Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3+56+ cells was also noted. Gene expression profiling on T cells from AML patients compared with healthy donors demonstrated global differences in transcription suggesting aberrant T-cell activation patterns. These gene expression changes differ from those observed in chronic lymphocytic leukemia (CLL), indicating the heterogeneous means by which different tumors evade the host immune response. However, in common with CLL, differentially regulated genes involved in actin cytoskeletal formation were identified, and therefore the ability of T cells from AML patients to form immunologic synapses was assessed. Although AML T cells could form conjugates with autologous blasts, their ability to form immune synapses and recruit phosphotyrosine signaling molecules to the synapse was significantly impaired. These findings identify T-cell dysfunction in AML that may contribute to the failure of a host immune response against leukemic blasts. |
| Databáze: | OpenAIRE |
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