2014 Fiscal Year Final Research Report
Detection of leukemogenic and paraleukemic target genes for childhood leukemic chimeric transcription factor
| Project/Area Number |
23591549
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
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| Research Collaborator |
KIKUCHI Jiro
FURUKAWA Yusuke
INUKAI Takeshi
INABA Toshiya
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Keywords | 小児白血病 / PTHｒP / E2A-HLF / アポトーシス |
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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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| Free Research Field |
小児白血病
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