Monoclonal antibodies specific to the acute lymphoblastic leukemia t(1;19)-associated E2A/pbx1 chimeric protein: Characterization and diagnostic utility

• Published in: Blood Vol. 89; no. 8; pp. 2909 - 2914
• Main Authors: SANG, B.-C, SHI, L, DIAS, P, LIU, L, WEI, J, WANG, Z.-X, MONELL, C. R, BEHM, F, GRUENWALD, S
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.04.1997
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Neoplasm - immunology; Antigens, Neoplasm - analysis; Antigens, Neoplasm - immunology; Biological and medical sciences; Bone Marrow - pathology; Burkitt Lymphoma - immunology; Burkitt Lymphoma - pathology; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 1 - ultrastructure; Chromosomes, Human, Pair 19 - genetics; Chromosomes, Human, Pair 19 - ultrastructure; Female; Hematologic and hematopoietic diseases; Homeodomain Proteins - analysis; Homeodomain Proteins - immunology; Humans; Leukemia-Lymphoma, Adult T-Cell - diagnosis; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemia-Lymphoma, Adult T-Cell - immunology; Leukemia-Lymphoma, Adult T-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neoplastic Stem Cells - immunology; Oncogene Proteins, Fusion - analysis; Oncogene Proteins, Fusion - immunology; Peptide Fragments - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Translocation, Genetic; Tumor Cells, Cultured; Chromosomal aberration; Human; Acute; Malignant hemopathy; Monoclonal antibody; Abnormal chromosome F19; Lymphoproliferative syndrome; C-Onc gene; Abnormal chromosome A1; Cytogenetics; Abnormal chromosome; Diagnosis; Acute lymphocytic leukemia; Hybrid gene; Homeobox sequence; Chromosome translocation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v89.8.2909

Nonrandom chromosomal abnormalities are found in most human malignancies, particularly leukemias and lymphomas. A characteristic t(1;19) (q23;p13.3) chromosomal translocation is detected in 5% of childhood acute lymphoblastic leukemia (ALL) cases. This translocation results in the formation of a fusion gene, which leads to the expression of an oncogenic E2A/pbx1 protein. Breakpoints in the E2A gene almost invariably occur within a single intron, and the identical portion of PBX1 is joined consistently to exon 13 of E2A in fusion mRNA. In this article, we report the development of monoclonal antibodies against E2A/pbx1 fusion protein using a specific peptide that corresponds to the junction region of the protein. The obtained antibodies recognize specifically the chimeric E2A/pbx1 fusion protein and lack cross-reactivities with E2A and pbx1. Immunohistochemical staining and flow cytometric studies show that these antibodies can distinguish t(1;19)-positive from t(1;19)-negative leukemic cells. These results indicate that the obtained E2A/pbx1-specific monoclonal antibodies might prove to be valuable diagnostic reagents and important tools for elucidating the mechanisms involved in oncogenesis and progression of t(1;19)-positive childhood ALL.