Bj. Longley et al., Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy, LEUK RES, 25(7), 2001, pp. 571-576
Mutations causing constitutive activation of KIT have been shown to be caus
ative in some forms of mastocytosis, and several types of mutations have be
en associated with myeloproliferative disorders (MPDs), acute myelogenous l
eukemia (AML), sinonasal lymphomas, and gastrointestinal stromal tumors (GI
ST). We divide these activating mutation into two types - 'regulatory type'
mutations, which affect regulation of the kinase molecule, and 'enzymatic
pocket type' mutations, which alter the amino acid sequence directly formin
g the enzymatic site. KIT inhibitors have been suggested as therapeutic dru
gs for these conditions, but different types of activating mutations respon
d differentially to KIT inhibitors, so classification of individuals on the
basis of specific mutations is necessary to guide therapy. (C) 2001 Elsevi
er Science Ltd. All rights reserved.