Identification of translocational breakpoints within the intron region before the last coding exon (exon 12) of the EVI1 gene in two cases of CML-BC with inv(3)(q21q26).
We have previously shown that the EVI1 gene at chromosome 3q26 is transcriptionally activated by chromosomal rearrangements in acute myelogenous leukemias (AMLs) with inv(3)(q21q26) or t(3;3)(q21;q26). The breakpoints in t(3;3) cases were 15 to 330 kb upstream of the EVI1 gene, while those in inv(3) cases were 150 to 200 kb downstream and outside of the EVI1 coding region. The EVI1 gene is also activated in chronic myelogenous leukemia-blastic crisis (CML-BC) with inv(3)(q21q26); however, the molecular mechanism of EVI1 activation in CML-BC is still unclear. In this paper, we have analyzed chromosomal rearrangements in two leukemia cell lines derived from CML-BC with inv(3)(q21q26) and have identified the breakpoints within the EVI1 coding area. The EVI1 gene spans over 100 kb with 12 exons (10 coding exons), and the chromosomal breakpoints are clustered in the intron region before the last coding exon (exon 12). The nucleotide sequence of EVI1 cDNA clones from MOLM-1 cells was truncated at exon 11, and a novel sequence of 681 nucleotides was added at the 3' end of the EVI1 transcripts. The novel sequence was derived from a readthrough intron sequence 3' to the coding exon 11 adjacent to the breakpoint. The breakpoints at 3q21 were within the breakpoint cluster area downstream of the ribophorin I gene, suggesting that the activation mechanism of the EVI1 gene in CMLs with inv(3) is the same as that in AMLs with inv(3). These results indicate that expression of a truncated EVI1 gene is an important factor in the progression of CML.
Suzukawa
K
K
Biology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Taki
T
T
Abe
T
T
Asoh
H
H
Kamada
N
N
Yokota
J
J
Morishita
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D015321:Gene Rearrangement; D006801:Humans; D007438:Introns; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D000074008:MDS1 and EVI1 Complex Locus Protein; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D014157:Transcription Factors; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors