| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
The E2A-HLF fusion transcription factor generated by t(17;19)(q22;p13) translocation is found in pro-B cell acute lymphoblastic leukemias (ALLs) and promotes leukemogenesis via antiapoptotic function, bone invasion, hypercalcemia and coagulopathy. Here, we demonstrate that t(17;19)+ ALL cells express PTHrP at high levels when compared with other ALL cells. Forced expression of E2A-HLF in t(17;19)- ALL cells up-regulated PTHrP expression, while transactivation domain mutants of E2A or basic domain mutants of HLF did not show PTHrP expression in t(17;19)- ALL cells. These results suggest that PTHrP is a downstream target of E2A-HLF. PTHrP knockdown by the shRNA lentivirus system induced sub-G0G1 and G0G1 accumulation indicating apoptosis in t(17;19)+ ALL cells. These data indicate that PTHrP expression, which is induced by E2A-HLF, is a key element in the protection of t(17;19)+ ALL cells from apoptosis and in the induction of bone invasion and hypercalcemia.
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