title: Identification of kit(M541L) somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response.
abstract: Activating mutations of KIT receptor tyrosine kinase have been reported in different neoplasms. The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. We investigated the presence of KIT(M541L) in five males with chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), all negative for Platelet-derived growth factor-alpha (PDGFR) or PDGFRbeta abnormalities, which responded to imatinib therapy. To assess whether the mutation was constitutive or somatic in nature, we evaluated its presence analyzing either the neoplastic or normal cell population (epidermal cells or CD3-positive T lymphocytes). KIT(M541L) substitution was found in 4 out of 5 patients and in all it was somatic in nature. All patients were treated with low dose imatinib (100 mg daily orally), achieving complete and persistent clinical and hematological remission (median follow-up 74 months). One patient relapsed after 50 months. Our study strongly suggests to search for the KIT(M541L) in patients with CEL, NOS, negative for PDGFRalpha and PDGFRbeta abnormalities, to identify a subgroup of cases who may benefit from low dose imatinib therapy.
authors.affiliation: Hematology and Transplantation Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; Oncohematology Unit of the Elderly, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Beghini
authors.forename: Orietta
authors.initials: O
authors.lastname: Spinelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Orofino
authors.forename: Francesca
authors.initials: F
authors.lastname: Lazzaroni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cambiaghi
authors.forename: Tamara
authors.initials: T
authors.lastname: Intermesoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
mesh_terms: D000293:Adolescent; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000235:genetics*; D000068877:Imatinib Mesylate; D059785:Karyotype; D007938:Leukemia; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha