RAS and CSF3R mutations in severe congenital neutropenia.

摘要

Severe congenital neutropenia (CN), a congenital disorder of hematopoiesis and a preleukemic predisposition, has been used as a model for multistep pathogenesis of leukemia. CSF3R gene mutations are regarded as an early marker of malignant transformation in CN.1-2 A commonly accepted model is that the acquisition of CSF3R mutations, which confer a growth advantage to myeloid progenitors,3 is an early and specific event, typically followed by other nonspecific genetic changes necessary for complete transformation. Common genetic abnormalities like acquired clonal cytoge-netic alterations or activating RAS mutations5 have also been observed to be associated with CN-related myelodysplastic syndrome (MDS)/leukemia. The assumption of RAS mutations as frequent genetic aberrations in the malignant transformation of CN67 is mainly based on the original study on RAS mutations in CN by Kalra et al5 (5/11 patients with CN and MDS/leukemia).