title: High frequency of fusion transcripts of exon 11 and exon 4/5 in AF-4 gene is observed in cord blood, as well as leukemic cells from infant leukemia patients with t(4;11)(q21;q23).
abstract: The MLL gene located on chromosome 11q23 and its translocation to the AF-4 gene located on chromosome 4q21 play a pivotal role in leukemogenesis in infancy. Studies of identical leukemic twins have provided evidence of the MLL rearrangement as a fetal event during pregnancy. We analyzed the presence and frequency of the MLL/AF-4 rearrangement in normal cord blood. Although no chimeric mRNA of MLL or AF-4 was detected in 65 cord blood samples, in-frame fusion transcripts of exon 11 and exon 4 or 5 of the AF-4 gene were detected in three of the samples by a nested polymerase chain reaction. When primers of exon 11 and exon 5 of the AF-4 gene were used, two forms of fusion transcripts (AF-4 exon 11/4 or exon 11/5) were detected in 20 of the 65 cord blood samples (31%) and also four of six leukemic cell samples with t(4;11) (67%), whereas such transcripts were not observed in any of 21 peripheral blood samples nor in fetal fibroblasts. These findings suggest that the in-frame fusion of exon 11 and exon 4 or 5 of the AF-4 gene frequently occurs in hematopoietic cells during the intrauterine period, even in a healthy fetus. Although it is unknown whether the proteins of the AF-4 fusion transcripts have some functions, the instability of the AF-4 gene may be associated with the leukemogenesis of infant leukemia.
authors.affiliation: Department of Pediatrics, Saga Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Zaitsu
authors.forename: E
authors.initials: E
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Yatsuki
authors.forename: S
authors.initials: S
authors.lastname: Mizutani
authors.forename: M
authors.initials: M
authors.lastname: Eguchi
authors.forename: K
authors.initials: K
authors.lastname: Ihara
authors.forename: T
authors.initials: T
authors.lastname: Okamura
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
mesh_terms: D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D005091:Exons / Q000235:genetics; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000032:analysis* / Q000097:blood; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000097:blood; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014178:Translocation, Genetic
chemical_list: C113855:MLL-AF4 fusion protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D051788:Myeloid-Lymphoid Leukemia Protein