Chromosomal translocation t (1; 19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor

J Nourse, JD Mellentin, N Galili, J Wilkinson… - Cell, 1990 - cell.com
J Nourse, JD Mellentin, N Galili, J Wilkinson, E Stanbridge, SD Smith, ML Cleary
Cell, 1990cell.com
The gene (E2A) for enhancer binding transcription factors El2 and E47 maps to the t (1; 19)
chromosomal translocation breakpoint in pre-B cell leukemias. Altered E2A transcripts
lacking sequences coding for the helix-loop-helix DNA binding motif were detected in
several t (l; l9)-carrying cell lines. Fusion cDNAs that crossed the t (1; 19) breakpoint were
cloned and shown to code for an 85 kd protein consisting of the aminoterminal two-thirds of
E2A fused to a chromosome l-derived protein. The fusion protein has the features of a …
Summary
The gene (E2A) for enhancer binding transcription factors El2 and E47 maps to the t (1; 19) chromosomal translocation breakpoint in pre-B cell leukemias. Altered E2A transcripts lacking sequences coding for the helix-loop-helix DNA binding motif were detected in several t (l; l9)-carrying cell lines. Fusion cDNAs that crossed the t (1; 19) breakpoint were cloned and shown to code for an 85 kd protein consisting of the aminoterminal two-thirds of E2A fused to a chromosome l-derived protein. The fusion protein has the features of a chimeric transcription factor in which the DNA binding domain of E2A is replaced by the putative DNA binding domain of a homeoprotein from chromosome 1 for which the name Prl (pre-6 cell leukemia) is proposed. Identical E2A-prl mRNA junctions were detected by PCR in three t (1; 19)-carrying cell lines, indicating that the fusion transcripts and predicted chimeric protein are a consistent feature of this translocation.
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