title: Detection of HRX-FEL fusion transcripts in pre-pre-B-ALL with and without cytogenetic demonstration of t(4;11).
abstract: The t(4;11)(q21;q23) characterizes a distinct clinical entity of childhood and adult acute lymphoblastic leukemia (ALL) with a pre-pre-B-phenotype, monocytoid features, coexpression of CD15 and/or CDw65 and a dismal prognosis. The molecular correlate of the t(4;11) has been identified as a fusion transcript of HRX, a gene on 11q23 with homology to drosophila trithorax gene, and FEL, a serine-proline-rich gene on 4q21 of unknown function. The aim of the current study was to establish a reverse transcription-polymerase chain reaction (RT-PCR) approach for the rapid and sensitive detection of the HRX-FEL fusion transcript associated with the t(4;11). For this purpose, two groups of patients were studied: group A comprised cases with cytogenetically proven t(4;11) including three infant and four adult pre-pre-B-ALL, as well as the two cell lines RS4;11 and MV4;11. Group B consisted of ten adult pre-pre-B-ALL with the identical phenotype, but without cytogenetic confirmation of t(4;11). Using primers complementary to HRX and FEL cDNA sequences 300 to 500 bp 5' and 3' of published breakpoints, respectively, specific amplification products were obtained in all nine cases of group A and in nine of the ten cases of group B. Three different types of fusion transcripts were identified by sequence analysis with HRX breakpoints at nucleotides 4086 and 4218 and FEL breakpoints at nucleotides 1413, 1416, and 1458. These data indicate that RT-PCR allows the detection of HRX-FEL fusion transcripts in the vast majority of cytogenetically proven and immunophenotypically suspected t(4;11) ALL. Hence, this technique may allow identification of a further subset of high risk ALL and may also be useful for the monitoring of minimal residual disease in t(4;11) ALL.
authors.affiliation: Department of Internal Medicine, University of Göttingen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Griesinger
authors.forename: H
authors.initials: H
authors.lastname: Elfers
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: M
authors.initials: M
authors.lastname: Falk
authors.forename: H
authors.initials: H
authors.lastname: Rieder
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.forename: F
authors.initials: F
authors.lastname: Lampert
authors.forename: B
authors.initials: B
authors.lastname: Heinze
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: E
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001483:Base Sequence; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D006801:Humans; D016256:Lewis X Antigen; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D016256:Lewis X Antigen; D009363:Neoplasm Proteins