|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1997 : ¥2,100,000 (Direct Cost : ¥2,100,000)
Using FISH with 13 cosmid probes (tel--FB12-CA5-G7-FD2- CB1 -ED8-FD9-G32-AE3-G50-AD8-GG4-PEBP2_C--cen), we have determined the 1p36 breakpoint of t(1 ; 3)(p36 ; q21) translocation in four myelodysplastic syndrome (MDS) patients and one adult-type CML patient : the breakpoint was between CA5 and G7 (1p36.3) in four MDS patients and between GG4-PEBP2αC (1p36.1) in the CML patient. This indicated that the 1p36 breakpoint was different between different disorders. As a next step, we made a contig map between CA5 and G7 using a total of 33 BAC clones. The breakpoints of three MDS patients were found in PAC163G9 clone, and that of the remaining MDS patient was found in BAC737N8, suggesting that the 1p36 breakpoint in MDS may be scattered in 340 kb region at most, since BAC clone generally cover ca 170kb. Now, we are searching all the genes contained in the two clones through DNA sequencing to find out the responsible gene for MDS.
On the other hand, Mochizuki, et al. reported that they found out responsible genes for t(1 ; 3)(p36 ; q21) translocation (Mochizuki N, et al : A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS/EVI1 gene and is transcriptionally activated in t(1 ; 3)(p36 ; q21)-positive leukemia cells. Blood 96 : 3209, 2000) : MEL1 gene located adjacent to the 1p36 breakpoint was transcriptionally activated by the promoter of Evi1 gene located adjacent to the 3q21 breakpoint only in t(1 ; 3)(p36 ; q21)-positive leukemia cells. We also studied whether the MEL1 gene was expressed in two MDS patients of our series. We found that PRDM16 gene, not MEL1, which shows highly homology to MEL1 with only difference in 3' end was highly expressed although this gene was not expressed in any other cell lines (in preparation).