2004 Fiscal Year Final Research Report Summary
Mechanisms in hematopoiesis and leukemogenesis by the transcription factor TEL
| Project/Area Number |
14370308
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Dokkyo Medical University |
|---|
Principal Investigator |
MITANI Kinuko Dokkyo Medical University School of Medicine, Department of Hematology, Professor, 医学部, 教授 (50251244)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
WAGA Kazuo Dokkyo Medical University School of Medicine, Department of Hematology, Lecturer, 医学部, 講師 (00285917)
SASAKI Ko Dokkyo Medical University School of Medicine, Department of Hematology, Assistant Professor, 医学部, 助手 (60282638)
MAKI Kazuhiro Dokkyo Medical University School of Medicine, Department of Hematology, Assistant Professor, 医学部, 助手 (50337391)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | TEL / TEL / AML1 / TEL / PTPRR / transcription factor / leukemia / chromosomal abnormality / ERK / isoform |
|---|
| Research Abstract |
Regulation in hematopoiesis by TEL.
(1)We demonstrated that TEL stimulates the erythroid differentiation induced by chemical compounds hemin and DMSO in murine erythroleukemia MEL cells. To confirm this TEL's effect in a more physiological setting, we introduced TEL cDNA into human leukemia UT7/GM cells. TEL accelerated the erythroid differentiation induced by erythropoietin and inhibited the megakaryocytic differentiation induced by thrombopoietin. These data suggest that TEL could decide the cell fate in differentiation in erythroid/megakaryocytic common progenitor.
(2)We also examined regulatory mechanisms in the TEL's function. TEL was found to be phosphorylated by the MAP kinase ERK. Hyperphosphorylated TEL lost its transcription repressive ability and tumor suppressive function, and exerted dominant-negative effect over hypophosphorylated TEL. On the other hand, various types of isoform were observed expressed from the TEL gene. Among them, ΔHLH and ΔETS isoforms were dominant-inhibitory molecules for wild-type TEL. We showed that expression frequency of ΔETS isoform was increased in myelodysplastic syndrome-derived leukemia in comparison to myelodysplastic syndrome in early phase.
Mechanism in leukemogenesis by TEL.
(1)TEL/AML1 generated by t(12;21) in childhood pre-B cell acute lymphoblastic leukemia is known to dominantly repress wild-type AML1's function. We showed that TEL/AML1 also inhibits wild-type TEL's function. Loss of tumor suppressive function from TEL could pay a causative role in leukemogenesis by t(12;21).
(2)We cloned a novel TEL/PTPRR chimeric gene generated by inv(12) in acute myelogenous leukemia. TEL/PTPRR had dominant-negative function over wild-type TEL in molecular assays. Furthermore, UT7/GM cells overexpressing TEL/PTPRR acquired factor-independent growth, and maintained high level of phosphorylation in STAT3 even after factor withdrawal. We conclude that TEL/PTPRR causes leukemia through inactivating TEL and stimulating STAT3 signal.
|
-
-
-
-
-
-
-
[Journal Article] Dysplastic definitive hematopoiesis in AML1/Evi-1 knock-in embryos.2005
Author(s)
Maki, K., Yamagata, T., Asai, T., Yamazaki, I., Oda, H., Hirai, H., Mitani, K.
-
Journal Title
Blood 106
Pages: 2147-2155
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance.2005
Author(s)
Seo, S., Asai, T., Saito, T., Suzuki, T., Morishita, Y., Nakamoto, T., Ichikawa, M., Yamamoto, G., Kawazu, M., Yamagata, T., Sakai, R., Mitani, K., Ogawa, S., Chiba, S., Hirai, H.
-
Journal Title
J Immunol 75
Pages: 3492-3501
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] The corepressor mSin3A regulates phosphorylation-induced activation, intranuclear location, and stability of AML1.2004
Author(s)
Imai, Y., Kurokawa, M., Yamaguchi, Y., Izutsu, K., Nitta, E., Mitani K., Satake, M., Noda, T., Ito, Y., Hirai, H.
-
Journal Title
Mol Cell Biol 24
Pages: 1033-1043
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Leukemia-related transcription factor TEL is negatively regulated through ERK-induced phosphorylation.2004
Author(s)
Maki, K., Arai, H., Waga, K., Sasaki, K., Nakamura, F., Imai, Y., Kurokawa, M., Hirai, H., Mitani K.
-
Journal Title
Mol Cell Biol 24
Pages: 3227-3237
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] AML1 is functionally regulated through p300-mediated acetylation on specific lysine residues.2004
Author(s)
Yamaguchi, Y., Kurokawa, M., Imai, Y., Izutsu, K., Asai, T., Ichikawa, M., Yamamoto, G., Nitta, E., Yamagata, T., Sasaki, K., Mitani K., Ogawa, S., Chiba, S., Hirai, H.
-
Journal Title
J Biol Chem 279
Pages: 15630-15638
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis.2004
Author(s)
Ichikawa, M., Asai, T., Saito, T., Yamamoto, G., Seo, S., Yamazaki, I., Yamagata, T., Mitani K., Chiba, S., Ogawa, S., Kurokawa, M., Hirai, H.
-
Journal Title
Nat Med 10
Pages: 299-304
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Functional analysis of a dominant-negative DETS TEL/ETV6 isoform.2004
Author(s)
Sasaki, K., Nakamura, Y., Maki, K., Waga, K., Nakamura, F., Arai, H., Imai, Y., Hirai, H., Mitani, K.
-
Journal Title
Biochem Biophys Res Comm 317
Pages: 1128-1137
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] TEL/AML1 shows dominant-negative effects over TEL as well as AML1.2004
Author(s)
Gunji, H., Waga, K., Nakamura, F., Maki, K., Sasaki, K., Nakamura, Y., Mitani, K.
-
Journal Title
Biochem Biophys Res Comm 322
Pages: 623-630
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] The transcriptionally active form of AML1 is required for hematopoietic rescue of the AML1-deficient embryonic para-aortic splanchnopleural (P-Sp) region.2004
Author(s)
Goyama, S., Yamaguchi, Y., Imai, Y., Kawazu, M., Nakagawa, M., Asai, T., Kumano, K., Mitani, K., Ogawa, S., Chiba, S., Kurokawa, M., Hirai, H.
-
Journal Title
Blood 104
Pages: 3558-3564
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Functional domains of Runx1 are differentially required for CD4 repression, TCRb, and CD4/9 double negative to CD4/8 double positive transition in thymocyte development.2004
Author(s)
Kawazu, M., Asai, T., Ichikawa, M., Yamamoto, G., Saito, T., Goyama, S., Mitani, K., Miyazono, K., Chiba, S., Ogawa, S., Kurokawa, M., Hirai, H.
-
Journal Title
J Immunol 174
Pages: 3526-3533
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
[Journal Article] Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells.2003
Author(s)
Waga, K., Nakamura, Y., Maki, K., Arai, H., Yamagata, T., Sasaki, K., Kurokawa, M., Hirai, H., Mitani K.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Should young patients with e19a2 type BCR/ABL rearrangement undergo stem cell transplantation.2003
Author(s)
Nakamura, F., Ogawa, S., Izutsu, K., Imai, Y., Maki, K., Yamagata, T., Mitani, K., Hirai, H.
-
Journal Title
Leuk & Lymph 44
Pages: 381-382
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis.2003
Author(s)
Qiao, Y., Ogawa, S., Hangaishi, A., Yuji, K., Izutsu, K., Kunisato, A., Imai, Y., Wang, L., Hosoya, N., Nannyg, Y., Sato, Y., Maki, K., Mitani K., Hirai, H.
-
Journal Title
Leukemia 17
Pages: 1112-1120
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
[Journal Article] The t(3 ; 21) fusion product, AML1/Evi-1, blocks AML1-induced transactivation by recruiting CtBP.2002
Author(s)
Izutsu, K., Kurokawa, M., Imai, Y., Ichikawa, M., Asai, T., Maki, K., Mitani K., Hirai, H.
-
Journal Title
Oncogene 21
Pages: 2695-2703
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Mutational analyses of the AML1 gene in patients with myelodysplastic syndrome.2002
Author(s)
Imai, Y., Kurokawa, M., Izutsu, K., Hangaishi, A., Maki, K., Ogawa, S., Chiba, S., Mitani K., Hirai, H.
-
Journal Title
Leuk & Lymph 43
Pages: 617-621
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] N-ras and p53 gene mutations in Japanese patients with myelo-proliferative disorders.2002
Author(s)
Tsurumi, S., Nakamura, Y., Maki, M., Omine, M., Fujita, K., Okamura, T., Niho, Y., Hashimoto, S., Kanno, K., Suzuki, K., Hangaishi, A., Ogawa, S., Hirai, H.Mitani, K.
-
Journal Title
Am J Hematol 71
Pages: 131-133
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Functional regulation of TEL by p38-induced phosphorylation.2002
Author(s)
Arai, H., Maki, K., Waga, K., Sasaki, K., Nakamura, Y., Imai, Y., Kurokawa, M.,.Hirai, H., Mitani, K.
-
Journal Title
Biochem Biophys Res Comm 299
Pages: 116-125
Description
「研究成果報告書概要(欧文)」より
