Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

Abstract

Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense.

• Authors: P Yotnda, F Garcia, M Peuchmaur, B Grandchamp, M Duval, F Lemonnier, E Vilmer, P Langlade-Demoyen
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 102 Issue 2 Pg. 455-62 (Jul 15 1998) ISSN: 0021-9738 [Print] United States
• PMID: 9664088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Core Binding Factor Alpha 2 Subunit
• HLA-A2 Antigen
• Neoplasm Proteins
• Oncogene Proteins, Fusion
• Peptides
• Recombinant Fusion Proteins
• TEL-AML1 fusion protein

Topics

• Amino Acid Sequence
• Cell Line
• Child
• Child, Preschool
• Core Binding Factor Alpha 2 Subunit
• Cytotoxicity Tests, Immunologic
• Female
• HLA-A2 Antigen (immunology, metabolism)
• Humans
• Male
• Molecular Sequence Data
• Neoplasm Proteins (genetics, immunology)
• Oncogene Proteins, Fusion
• Peptides (chemical synthesis, immunology, metabolism)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (immunology)
• Recombinant Fusion Proteins (genetics, immunology)
• T-Lymphocytes, Cytotoxic (immunology)