Мастоцитоз - группа редких клональных расстройств, характеризующихся аномальной пролиферацией и накоплением неопластических тучных клеток в коже и/или различных внутренних органах. Несмотря на гетерогенность клинической картины и прогноза подтипов заболевания, ведущее звено в патогенезе мастоцитоза занимают молекулярно-генетические дефекты. Практически у всех пациентов с мастоцитозом обнаруживаются мутации в нуклеотидной последовательности гена KIT, чаще всего в виде замены аспарагиновой кислоты на валин в кодоне 816. Данные дефекты наблюдаются как при формах, характеризующихся благоприятным прогнозом, так и при злокачественных подтипах заболевания. Наличие других мутаций, например, в генах TET2, SRSF2, ASXL1, RUNX1, и молекулярно-генетических изменений, вызванных ими, вносят вклад в клинико-патологическое разнообразие мастоцитоза и ассоциировано с более агрессивным течением заболевания. Понимание сложности молекулярно-генетических изменений при мастоцитозе необходимо для выбора наиболее эффективного метода лечения и разработки новых препаратов, способных улучшить прогноз у пациентов c мастоцитозом. В статье представлены основные патогенетические механизмы мастоцитоза. Рассмотрена роль мутаций в гене KIT, а также индуцированные мутациями изменения в рецепторе с-Kit и внутриклеточных сигнальных путях, ответственных за пролиферацию тучных клеток. Mastocytosis is a group of rare clonal disorders characterized by abnormal proliferation and accumulation of neoplastic mast cells in the skin and/or various internal organs. Molecular genetic defects play the leading role in the pathogenesis of mastocytosis despite a significant clinical and prognostic heterogeneity of different forms of this disease. In almost all forms of mastocytosis, patients carry KIT gene mutations, mostly D816V. However, these defects are observed both in forms with good prognosis and in advanced variants of the disease. Mutations in other genes, such as TET2, SRSF2, ASXL1, RUNX1, and the resulting molecular changes contribute to the clinical and pathological heterogeneity of mastocytosis and are associated with a more aggressive disease. Insight into the complexity of molecular and genetic changes in mastocytosis is essential for choosing an optimum treatment and for developing new drugs to improve the outcome of the treatment. The article described major pathogenetic mechanisms of mastocytosis and focused on the role of KIT mutations, conformation of the c-Kit receptor, and intracellular signaling pathways responsible for the proliferation of mast cells.
Mastocytosis is a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs) in the skin and/or other organ systems. Mastocytosis is a rare disease. The annual incidence is 5–10 cases per 1 million people. However, the majority of cases stay undiagnosed due to the lack of specific tests and a wide variety of clinical features of the disease. In mastocytosis, somatic mutations of KIT gene lead to autocrine dysregulation and constitutive c-KIT activation in the absence of its ligand SCF. Clinical symptoms of the disease are determined by MC mediator release and/or infiltration of tissues by MCs. According to the World Health Organisation classification updated in 2016 mastocytosis is divided to cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), SM with an associated hematologic (non-MC-lineage) neoplasm (SMAHN), aggressive SM (ASM), MC leukemia (MCL) and MC sarcoma (MCS). The CM and ISM prognosis is excellent with (almost) normal life expectancy, unlike aggressive forms (ASM and MCL) with poor prognosis. In this paper the key aspects of clinical features and diagnostic criteria of mastocytosis are discussed. We present a case report of a patient with mastocytosis in the skin following psoralen plus ultraviolet A (PUVA) therapy with good response.
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