title: Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26).
abstract: Structural alterations occur in the long arm of chromosome 3 in approximately 2% of patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). The major alterations are inv(3)(q21q26) and t(3:3)(q21;q26) and are often classified as the 3q21q26 syndrome. We previously reported that the EVI1 gene is transcriptionally activated in AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) and that the chromosomal breakpoints at 3q26 in the translocations were 5' of the EVI1 gene, whereas the breakpoints in the inversion cases were 3' of the gene. In these studies, four additional cases of AML with inv(3)(q21q26) are shown to express the EVI1 gene and to have breakpoints 3' of the gene. To characterize the 3q21 breakpoint region, cosmid and phage clones were isolated that cover approximately 100 kb. At 3q21, the breakpoints for both AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) were found to cluster over a region of approximately 50 kb downstream of the Ribophorin I gene. The results indicate a common mechanism for the translocations and inversions and support the hypothesis that the transcriptional activation of the EVI1 gene is mediated by enhancer elements associated with the Ribophorin I gene.
authors.affiliation: Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Suzukawa
authors.forename: E
authors.initials: E
authors.lastname: Parganas
authors.forename: A
authors.initials: A
authors.lastname: Gajjar
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Tani
authors.forename: S
authors.initials: S
authors.lastname: Asano
authors.forename: H
authors.initials: H
authors.lastname: Asou
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: J
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D008565:Membrane Proteins; D014157:Transcription Factors; C034241:ribophorin