[Topoisomerase II inhibitors etoposide and doxorubicin induced rearrangement and fusion of AML1 gene].
OBJECTIVE
To investigate the relationship between topoisomerase II inhibitors and t(8;21) chromosomal translocation.


METHODS
The rearrangements of AML1 and ETO genes were detected by Southern Blot and the AML1-ETO fusion gene by nested RT-PCR combined with sequencing in K562 cells treated with etoposide (Vp16) and doxorubicin (DOX).


RESULTS
The rearrangements of AML1 gene were detectable after DOX treatment at concentrations of 10, 50 and 100 micro mol/L for 16 h, AML1-ETO fusion gene appeared after 50 micro mol/L DOX treatment for 48 h.


CONCLUSIONS
Induction of AML1 gene rearrangement and fusion by topoisomerase II inhibitors, represents one of the molecular mechanisms of t(8;21) chromosomal translocation.
Xiao
Zhi-jian
ZJ
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS and PUMC, Tianjin 300020, China.
D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015139:Blotting, Southern; D002470:Cell Survival / Q000187:drug effects; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D015321:Gene Rearrangement / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors / Q000235:genetics*
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors; D005047:Etoposide; D004317:Doxorubicin