Research Project
Grant-in-Aid for Scientific Research (B)
Monosomy 7 is a common nonrandom chromosomal abnormality found frequently in myelodysplastic syndrome (MDS) and related acute myeloid leukemia (AML). A previously uncharacterized genes, Miki, Titan Kasumi, were isolated from the site of a common microdeletion cluster in the 7q21 band. Mild protein localizes to the Golgi apparatus, centrosomes and mitotic spindles. Downregulation of Mild disturbs the maturation and positioning of centrosomes, resulting in unorganized spindles. Cells undergo pre-anaphase arrest and exit mitosis in the absence of chromosome segregation or terminate mitosis by cell death. In addition, chromosome instability is found in the progeny. The binding of Mild to spindles depends on the poly (ADP-ribose) polymerase activity of tankyrase-1. Titan-deficient mice looked normal. However, AML developed at very high frequency by infection of retrovirus and common integration sites were now establishing from these mice. These findings suggests that the three genes are promising candidates for long-sought responsible genes for -7/7q- in MDS and AML.
All 2008 2007 2006 Other
All Journal Article (17 results) (of which Peer Reviewed: 8 results) Presentation (30 results) Book (7 results)
Genes Cells. 13
Pages: 199-208
Genes to Cells 13
Blood (in press)
Genes Cells. (in press)
Mol. Cell 25
Pages: 99-112
Leukemia 21
Pages: 288-296
Mol.Cell 25.1
Leukemia 20
Pages: 635-644
Biochem.Biophys.Res.Commun. 344
Pages: 1023-1030
Pages: 288-96
