The NF1 gene protein product, neurofibromin, is a GTPase-activating protein (GAP) that inhibits RAS signaling by hydrolysis of active RAS-GTP into inactive RAS-GDP; therefore, NF1 deficiencies act as functional equivalents of activating mutations in RAS. The finding that the wild-type allele was lost in the bone marrow of children with JMML affected by neurofibromatosis type 1 established NF1 as a tumor suppressor gene [23]. Here, NF1 is linked to juvenile myelomonocytic leukemia.