Abstract:
:The pH chromosome, resulting from the t(9;22) translocation, is the most frequently observed cytogenetic aberration in acute lymphoblastic leukemia (ALL). Two genes, bcr and abl, are involved in this translocation. As a consequence, parts of the bcr and abl genes are fused, resulting in chimeric bcr-abl genes encoding chimeric BCR-ABL proteins. Three bcr-abl genes and proteins have been identified: e1-a2 P190bcr-abl, b2-a2 P210bcr-abl, and b3-a2 P210bcr-abl. Since these chimeric proteins only occur in Ph-chromosome-positive leukemic cells, they are by definition tumor-specific markers. Ph-chromosome-positive ALL is correlated with a bad prognosis, therefore the detection of chimeric BCR-ABL proteins is of prime importance in ALL diagnosis. In the present study, we report on the generation of a monoclonal antibody termed ER-FP1, raised against the tumor-specific e1-a2 BCR-ABL junction in P190bcr-abl. We show that ER-FP1 reacts highly specifically with e1-a2 P190bcr-abl in different assays. The reactivity of ER-FP1 with e1-a2 P190bcr-abl in soluble form was analyzed in an immunoprecipitation assay; specificity was confirmed by peptide inhibition studies. Binding of ER-FP1 to e1-a2 P190bcr-abl at the single cell level was detected by using immunofluorescence techniques. Immunological double-staining experiments using ER-FP1 and a monoclonal antibody recognizing all BCR-ABL proteins confirmed the specificity of ER-FP1 for the e1-a2 fusion point.
journal_name
Leukemiajournal_title
Leukemiaauthors
van Denderen J,ten Hacken P,Berendes P,Zegers N,Boersma W,Grosveld G,van Ewijk Wsubject
Has Abstractpub_date
1994-09-01 00:00:00pages
1503-9issue
9eissn
0887-6924issn
1476-5551journal_volume
8pub_type
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