6533b824fe1ef96bd12809c7
RESEARCH PRODUCT
A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells.
Thomas M. FischerMarkus P. RadsakFlorian H. HeidelCedrik M. BrittenStefan TenzerChristoph HuberClaudine GrafThomas WölfelFian K. Solemsubject
FLT3 Internal Tandem DuplicationMyeloidmedicine.medical_treatmentImmunologyAntigen presentationMolecular Sequence DataHuman leukocyte antigenBiologyCD8-Positive T-LymphocytesIn Vitro TechniquesTransfectionBiochemistryCell LineEpitopesfluids and secretionshemic and lymphatic diseasesCell Line TumorGene DuplicationGene duplicationmedicineCytotoxic T cellHumansAmino Acid SequenceRNA MessengerHLA-A1 AntigenAntigen PresentationHLA-A Antigenshemic and immune systemsCell BiologyHematologyImmunotherapymedicine.diseaseMolecular biologyLeukemiaLeukemia Myeloid Acutemedicine.anatomical_structurefms-Like Tyrosine Kinase 3embryonic structurespsychological phenomena and processesdescription
Abstract The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I–restricted immunogenic peptides. One of the tested peptides (YVDFREYEYY) induced in vitro autologous T-cell responses restricted by HLA-A*0101 that were also detectable ex vivo. These peptide-reactive T cells recognized targets transfected with the patient's FLT3-ITD, but not wild-type FLT3, and recognized the patient's AML cells. Our results demonstrate that AML leukemic blasts can in principle process and present immunogenic FLT3-ITD neoepitopes. Therefore, FLT3-ITD represents a potential candidate target antigen for the immunotherapy of AML.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-11-21 | Blood |