Monoclonal antibodies specific to the acute lymphoblastic leukemia
t(1;19)-associated E2A/pbx1 chimeric protein: characterization and
diagnostic utility
BC Sang, L Shi, P Dias, L Liu, J Wei, ZX Wang, CR Monell, F Behm and S Gruenwald
Department of Molecular and Cell Biology, PharMingen Inc, San Diego, CA
92121, USA.
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.
Volume 89,
Issue 8,
pp. 2909-2914,
04/15/1997
Copyright © 1997 by The American Society of Hematology
