title: Expression of identical E2A/PBX1 fusion transcripts occurs in both pre-B and early pre-B immunological subtypes of childhood acute lymphoblastic leukemia.
abstract: The translocation t(1;19)(q23;p13) in pediatric patients with acute lymphoblastic leukemia (ALL) was demonstrated in early reports to result in a consistent fusion between the E2A and PBX1 gene sequences and in the expression of a uniform, chimeric E2A/PBX1 mRNA with transforming potential. More recent observations suggested that cytogenetically identical t(1;19) translocations can result in the transcription of different mRNA species and that expression of the E2A/PBX1 message may be restricted to patients with the t(1;19) who display a pre-B phenotype of ALL. To further assess the correlation between the immunologic subtypes of the disease and specific genetic alterations, we have performed cytogenetic and molecular analyses in 221 children with B-lineage ALL. Expression of the chimeric E2A/PBX1 message was detected in 21 patients. Out of 14 patients, in whom cytoplasmic immunoglobulin (cig) analyses were available, no less than four had a cig- B-cell precursor ALL, whereas 10 displayed a cig+ B-ALL immunophenotype. These findings are at variance with a recent report in which expression of the E2A/PBX1 message was linked exclusively to a subset of patients who displayed a cig+ pre-B-cell precursor phenotype of ALL. In seven cases diagnosed before 1986, cig analyses were not available, and consequently E2A/PBX1 expression could not be correlated to a particular immunological subtype of B-cell precursor ALL. Our results have important implications for the detection of residual disease in pediatric patients where expression of the typical E2A/PBX1 mRNA may occur both in cig+ (pre-B) and cig- (early pre-B) immunologic subtypes of ALL.
authors.affiliation: Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Izraeli
authors.forename: T
authors.initials: T
authors.lastname: Henn
authors.forename: H
authors.initials: H
authors.lastname: Strobl
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: H
authors.initials: H
authors.lastname: Kovar
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: T
authors.initials: T
authors.lastname: Lion
mesh_terms: D002648:Child; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D003593:Cytoplasm / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D016130:Immunophenotyping; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics* / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger