Iurlo Alessandra, Gianelli Umberto, Beghini Alessandro, Spinelli Orietta, Orofino Nicola, Lazzaroni Francesca, Cambiaghi Stefano, Intermesoli Tamara, Rambaldi Alessandro, Cortelezzi Agostino
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.
Oncotarget. 2014 Jul 15;5(13):4665-70. doi: 10.18632/oncotarget.1941.
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.
KIT受体酪氨酸激酶的激活突变已在不同肿瘤中被报道。M541L KIT替代突变（KIT(M541L)）已被描述与儿童肥大细胞增多症相关，可提高受影响细胞的生长速率，并赋予对伊马替尼治疗更高的敏感性。我们调查了5例慢性嗜酸性粒细胞白血病患者（未另行说明的慢性嗜酸性粒细胞白血病，CEL，NOS）中KIT(M541L)的存在情况，这些患者血小板衍生生长因子α（PDGFR）或PDGFRβ均无异常，且对伊马替尼治疗有反应。为了评估该突变是组成性的还是体细胞性的，我们通过分析肿瘤细胞群体或正常细胞群体（表皮细胞或CD3阳性T淋巴细胞）来评估其存在情况。5例患者中有4例发现了KIT(M541L)替代突变，且均为体细胞性。所有患者均接受低剂量伊马替尼治疗（每日口服100 mg），实现了完全且持续的临床和血液学缓解（中位随访74个月）。1例患者在50个月后复发。我们的研究强烈建议在PDGFRα和PDGFRβ无异常的CEL，NOS患者中寻找KIT(M541L)，以识别可能从低剂量伊马替尼治疗中获益的病例亚组。
