The neurofibromatosis type 1 (NF1) tumor suppressor gene and myeloid leukemia

Activating mutations of RAS genes are a common event in the genesis of a wide variety of human tumor types (for review see Barbacid 1990). It has also become increasingly clear that many tumors without RAS gene mutations have acquired genetic lesions that contribute to tumorigenesis by causing increased or prolonged activation of Ras. In this paper we review and describe studies using human and mouse cells on the association between NF1 gene loss and the development of myeloid leukemia. The NF1 gene product, neurofibromin, has GTPase activating protein (GAP) activity for Ras and thus, could negatively regulate Ras. Therefore, NF1 gene loss in myeloid cells may contribute to leukemogenesis by activating Ras.