MONOCLONAL-ANTIBODIES SPECIFIC TO THE ACUTE LYMPHOBLASTIC-LEUKEMIA T(1-19)-ASSOCIATED E2A PBX1 CHIMERIC PROTEIN - CHARACTERIZATION AND DIAGNOSTIC UTILITY/

Nonrandom chromosomal abnormalities are found in most human malignanci es, particularly leukemias and lymphomas. A characteristic t(1:19) (q2 3; p13.3) chromosomal translocation is detected in 5% of childhood acu te lymphoblastic leukemia (ALL) cases. This translocation results in t he formation of a fusion gene, which leads to the expression of an onc ogenic E2A/pbx1 protein. Breakpoints in the E2A gene almost invariably occur within a single intron, and the identical portion of PBX1 is jo ined consistently to exon 13 of E2A in fusion mRNA. In this article, w e report the development of monoclonal antibodies against E2A/pbx1 fus ion 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 crossreactivities with E 2A and pbx1. Immunohistochemical staining and flow cytometric studies show that these antibodies can distinguish t(1:19)-positive from t(1:1 9)-negative leukemic cells. These results indicate that the obtained E SA/pbx1-specific monoclonal antibodies might prove to be valuable diag nostic reagents and important tools for elucidating the mechanisms inv olved in oncogenesis and progression of t(1;19)-positive childhood ALL . (C) 1997 by The American Society of Hematology.