Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.
The gene (E2A) for enhancer binding transcription factors E12 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(1;19)-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 amino-terminal two-thirds of E2A fused to a chromosome 1-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-B 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.
Nourse
J
J
Department of Pathology, Stanford University School of Medicine, California 94305.
Mellentin
J D
JD
Galili
N
N
Wilkinson
J
J
Stanbridge
E
E
Smith
S D
SD
Cleary
M L
ML
D000595:Amino Acid Sequence; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics; D002460:Cell Line; D002678:Chimera; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D005801:Genes, Homeobox; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D015342:DNA Probes; D004273:DNA, Neoplasm; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014157:Transcription Factors