title: The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias.
abstract: The t(1;19)(q23;p13) chromosomal translocation is observed cytogenetically in 25% of children with pre-B-cell acute lymphoblastic leukemia (ALL) and is associated with an adverse treatment outcome. The t(1;19) juxtaposes the E2A gene from chromosome 19 with the PBX1 gene on chromosome 1, leading to the production of fusion transcripts and resultant chimeric proteins that contain the transcriptional-activating motif of E2A and the DNA-binding homeodomain of PBX1. To investigate the molecular nature of E2A/PBX1 fusion in patients with t(1;19) ALL we used an RNA-based polymerase chain reaction (PCR) procedure to amplify a portion of the chimeric transcript. We detected E2A/PBX1 fusion transcripts in cells from 97% (37 of 38) of cases in which the t(1;19) had been observed cytogenetically. Molecular evidence of E2A/PBX1 fusion transcripts was also observed in a patient in whom a t(1;19) was not detected cytogenetically and in one patient with subclinical levels of minimal residual disease before overt clinical relapse. In all PCR-positive cases the junction of E2A and PBX1 coding sequences occurred at precisely the same location as demonstrated by hybridization of PCR products with a fusion site-specific detection oligonucleotide. These findings demonstrate the consistent fusion of E2A and PBX1 coding sequences resulting from t(1;19) and suggest that site-specific fusion of E2A and PBX1 is an important pathogenic event in t(1;19) ALL.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA.
authors.forename: S P
authors.initials: SP
authors.lastname: Hunger
authors.forename: N
authors.initials: N
authors.lastname: Galili
authors.forename: A J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: W M
authors.initials: WM
authors.lastname: Crist
authors.forename: M P
authors.initials: MP
authors.lastname: Link
authors.forename: M L
authors.initials: ML
authors.lastname: Cleary
mesh_terms: D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D005801:Genes, Homeobox; D006801:Humans; D008222:Lymphokines / Q000235:genetics; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D029584:Prostatic Secretory Proteins; D014178:Translocation, Genetic
chemical_list: D008222:Lymphokines; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors