Role of CREB in CML
Annual rept. 1 Feb 2006-31 Jan 2007
CALIFORNIA UNIV LOS ANGELES
Pagination or Media Count:
The purpose of this proposal is to understand the molecular pathways regulating Bcr-Abl positive CML cells. We demonstrated that the transcription factor, CREB, is highly expressed in K562 cells and cells from patients with chronic phase CML. This led us to hypothesize that CREB may play a critical role in regulating proliferation of CML cells. To determine whether CREB and CREB-dependent pathways may be bonafide targets for CML therapy, we chose to downregulate CREB using RNA interference. There are two specific aims. In Aim 1, we will test the hypothesis that downregulation of CREB inhibits proliferation and survival of CML cells. In Aim 2, will test the hypothesis that downregulation of CREB inhibits leukemia progression in vivo and in primary CML cells. We have generated CREB shRNA lentivirus and infected primary mouse and human bone marrow stem cells. We have also infected BaF3 cells expressing the T315I mutation of Bcr-Abl with and without CREB shRNA and followed leukemia progression in vivo. Our results suggest that CREB is necessary for both normal stem cell proliferation and differentiation, and leukemic progression.
- Anatomy and Physiology
- Medicine and Medical Research