2004 Fiscal Year Final Research Report Summary
Roles of GATA-2/retinoic acid receptor pathways and TEL-AML1 translocation in leukemia
| Project/Area Number |
15591037
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Aichi Cancer Center |
|---|
Principal Investigator |
TSUZUKI Shinobu Aichi Cancer Center, Division of Molecular Medicine, Senior Researcher, 遺伝子医療研究部, 主任研究員 (00342965)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | GATA-2 / retinoic acid receptor / leukemia / TEL-AML1 / pro-B cells |
|---|
| Research Abstract |
(1)Although abnormal retinoic acid receptors are known to cause leukemia, the mechanisms thereby are not clear. We have found retinoic acid receptors are capable of binding to transcription factor GATA-2,and through this interaction GATA-2 functions are rendered responsible to retinoic acid. These findings suggest that retinoic acid exert its action, in addition to canonical receptors, via GATA-2 factor that are normally expressed in immature hematopoietic cells. Indeed, we were able to show that colony formation activities of hematopoietic cells are affected by retinoic acid. Leukemia-associated abnormal retinoic acid receptors may disrupt normal GATA-2 functions, thus leading to leukemia.
(2)TEL-AML1 is a fusion gene generated as a result of t(12;21) chromosomal translocation, and the commonest genetic abnormality in child acute lymphocytic leukemia. This translocation is linked to pro-B cell leukemia, but the molecular mechanisms involved are not clear. We have modeled the TEL-AML1 translocation in mice and analyzed its function. The mice were found to have relative accumulation of pro-B cells at the expense of more differentiated stages of B cells, thus providing evidence that TEL-AML1 fusion gene product is capable of inhibiting B cell differentiation program. More detailed analysis is currently conducted.
|
Research Products
(7 results)
-
-
-
-
[Journal Article] Genome-wide array-based comparative genomic hybridization of diffuse large B-cell lymphoma : comparison between CD5-positive and CD5-negative cases.2004
Author(s)
Tagawa H, Tsuzuki S, Suzuki R, Karnan S, Ota A, Kameoka Y, Suguro M, Matsuo K, Yamaguchi M, Okamoto M, Morishima Y, Nakamura S, Seto M.
-
Journal Title
Cancer Res. 64(17)
Pages: 5948-5955
Description
「研究成果報告書概要(和文)」より
-
[Journal Article] Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma.2004
Author(s)
Kameoka Y, Tagawa H, Tsuzuki S, Karnan S, Ota A, Suguro M, Suzuki R, Yamaguchi M, Morishima Y, Nakamura S, Seto M.
-
Journal Title
Oncogene 23(56)
Pages: 9148-9154
Description
「研究成果報告書概要(和文)」より
-
-
