Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.
Bibliographical noteFunding Information:
The Children's Tumor Foundation provided generous support for KJM through the Young Investigator Award. Grants from the National Cancer Institute and the American Cancer Society (to DAL) supported this research. Packaging cells that contained the NF1-GRD retroviral vector were generously provided by Dr. D. Wade Clapp at the Indiana University Medical School.
- GAP-related domain
- Myeloid leukemia