Clinical Research Papers:
Identification of kitM541L somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response
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Alessandra Iurlo1,2, Umberto Gianelli3, Alessandro Beghini4, Orietta Spinelli5, Nicola Orofino1, Francesca Lazzaroni4, Stefano Cambiaghi6, Tamara Intermesoli5, Alessandro Rambaldi5 and Agostino Cortelezzi1
1 Hematology and Transplantation Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
2 Oncohematology Unit of the Elderly, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
3 Hematopathology Section, Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan Medical School and IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, Milan, Italy
4 Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
5 Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
6 Dermatology Unit, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, Milan, Italy
Alessandra Iurlo, email:
Keywords: Chronic Eosinophilic Leukemia, CEL-NOS, KIT541L, KIT mutation, Hypereosinophilic Syndrome.
Received: April 18, 2014 Accepted: April 30, 2014 Published: May 1, 2014
Activating mutations of KIT receptor tyrosine kinase have been reported in different neoplasms. The M541L KIT substitution (KITM541L) 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 KITM541L 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). KITM541L 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 KITM541L 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.
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