2000 Fiscal Year Final Research Report Summary
The pivotal role of apoptosis in leukemogenesis and chemo-sensitivity in childhood leukemias.
| Project/Area Number |
10470177
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Yamanashi Medical University |
|---|
Principal Investigator |
NAKAZAWA Shinpei Yamanashi Medical University Professor, 医学部, 教授 (90090034)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
GOI Kumiko Yamanashi Medical University Research Associate, 医学部, 助手 (70324192)
INUKAI Takeshi Yamanashi Medical University Research Associate, 医学部, 助手 (30293450)
SUGITA Kanji Yamanashi Medical University Assistant-Professor, 医学部, 講師 (60138055)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | Leukemia / Apoptosis / Chemotherapy / Translaocation / Transcriptin factor / Cytokine |
|---|
| Research Abstract |
Inhibition of apoptosis plays an important role in leukemogenesis and chemo-resistance of childhood leukemias. In this study, to provide clue for better therapeutic outcome in childhood leukemias, we have tried to verify the mechanism of leukemogenesis and chemo-resistance particularly by shedding light on apoptosis.
1.We found out the expression of PPARγ, member of the steroid receptor family, in the leukemic cells. In the presence of ligand, leukemic cells underwent apoptosis through the downregulation of c-myc expression, suggesting that PPARγligand is one of the novel candidates for chemotherapeutic agents for leukemias.
2.We tested the expression of the cytokine receptors in leukemic cells and found out that both G-CSF receptor and TPO receptor are frequently expressed in the leukemic cells derived in stem cell level, such as Ph1 -positive and 11q23-related translocation-positive leukemias. In the presence of G-CSF or TPO, the proliferation of several leukemic cells was activated, s
… More
uggesting that these cytokines enhance the pro-apoptotic activities of chemotherapeutic reagents.
3.We have identified a SLUG transcription factor gene as a downstream target of antiapototic activity of the E2A-HLF fusion transcription factor derived form t (17 ; 19) in childhood leukemias. We analyzed the configuration of human SLUG gene in comparison with that of mouse gene and found out that the region about 1kb upstream of major start site of human SLUG gene shows an extremely high identity in the sequence to that of mouse gene. EMSA using this region as a probe indicated the specific binding of E2A-HLF, suggesting that E2A-HLF directly upregulates the SLUG gene expression through this region.
4.We analyzed the apoptosis induced by the serum-deprivation in 11q23-related translocation-positive leukemias and found out that 6 out of 9 cell lines established in our laboratory showed the resistance in apoptosis, suggesting that anti-apoptoic features play an important role in the disease progression in this type of leukemia. Less
|
Research Products
(12 results)
-
-
-
-
-
-
-
-
-
[Publications] Sugita K, Mori T, Yokota S, Kuroki Ma, O-Koyama T, Inukai T, Iijima K, Goi K, Tezuka T, Kojika S, Shiraishi K, Nakamura M, Miyamoto N, Karakida N, Kagami K, Nakazawa S.: "The KOR-SA3544 antigen predominantly expressed on surface of Philadelphia chromosome-positive acute lymphoblastic cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells."Leukemia. 13. 779-785 (1999)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Nakamura M, Sugita K, Inukai T, Goi K, Iijima K, Tezuka T, Kojika S, Shiraishi K, Miyamoto N, Karakida N, Kagami K, O-Koyama T, Mori T, Nakazawa S.: "p16/MTS1/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q23 translocation."Leukemia. 13. 884-890 (1999)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look T.: "SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein."Mol Cell. 4. 343-352 (1999)
Description
「研究成果報告書概要(欧文)」より
