| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| 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.
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