2012 Fiscal Year Final Research Report
molecular mechanisms supporting minimal-residual disease of 11q23/MLL-rearranged leukemia cells in bone marrow
| Project/Area Number |
22591153
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Yamanashi |
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Principal Investigator |
FURUICHI Yoshiyuki 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (20467137)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 11q23 転座型 ALL / 微少残存病変(MRD) / FLT3-ligand(FL) / TGF-beta1 / 骨髄ストローマ細胞 / FOXO |
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| Research Abstract |
FLT3 is highly expressed in acute lymphoblastic leukemia with the 11q23/MLL rearrangement refractory to chemotherapy. The FLT3/FLT3-ligand (FL) interaction between 11q23/MLL-rearranged leukemia cells and bone marrow stromal cells expressing FL at high levels induce 11q23/MLL-rearranged leukemia cells into dormant status resistant to anti-leukemic agents. TGF-beta1 and FL cooperatively induce TGF-beta1-mRNA expression of 11q23/MLL-rearranged leukemia cells. Moreover, TGF-beta1 secreted by both bone marrow stromal cells and leukemia cells induce 11q23/MLL-rearranged leukemia into dormant status more strongly in cooperation with FL. Nuclear localization of forkhead O transcription factors (FOXO3a), that plays an important role in the maintenance of chronic myeloid leukemia stem cells, is decreased by stimulation of TGF-beta1 and FL in 11q23/MLL-rearranged leukemia cells.
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