Аллогенная трансплантация гемопоэтических стволовых клеток при острых миелоидных лейкозах: прогностическое значение сложного кариотипа, включающего аномалии del(5q), –7, del(7q)

Т.Л. Гиндина, Н.Н. Мамаев, С.Н. Бондаренко, Е.С. Николаева, И.А. Петрова, О.А. Слесарчук, А.С. Боровкова, С.В. Разумова, А.Л. Алянский, Л.С. Зубаровская, Б.В. Афанасьев

НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Татьяна Леонидовна Гиндина, канд. мед. наук, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; тел.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

Для цитирования: Гиндина Т.Л., Мамаев Н.Н., Бондаренко С.Н. и др. Аллогенная трансплантация гемопоэтических стволовых клеток при острых миелоидных лейкозах: прогностическое значение сложного кариотипа, включающего аномалии del(5q), –7, del(7q). Клиническая онкогематология. 2016;9(3):271-78.

DOI: 10.21320/2500-2139-2016-9-3-271-278


РЕФЕРАТ

Цель. Оценить прогностическое значение сложного кариотипа, включающего аномалии del(5q), –7, del(7q) при острых миелоидных лейкозах (ОМЛ) у больных после аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК).

Материалы и методы. Обследовано 44 больных ОМЛ с аномалиями хромосомы 5 и/или 7 (22 женского и 22 мужского пола в возрасте от 1,2 до 67 лет, медиана 31,2 года). Проведен анализ предикторов общей (ОВ) и бессобытийной выживаемости (БСВ) после аллоТГСК у больных с различными клиническими, трансплантационными и цитогенетическими характеристиками.

Результаты. До аллоТГСК сложный кариотип (³ 3 хромосомных нарушений) был выявлен у 19 (43 %) больных, моносомный кариотип — у 8 (18 %). По данным однофакторного анализа, показатели ОВ и БСВ после аллоТГСК отличались у больных различных возрастных групп (³ 18 vs < 18 лет; = 0,01 и = 0,05 соответственно), с различным клиническим статусом болезни на момент трансплантации (1 ремиссия vs другой статус; = 0,1 и = 0,008 соответственно), со сложным кариотипом и без такового (СК– vs СК+; = 0,05 и = 0,002 соответственно), с моносомным кариотипом и без такового (МК+ vs МК–; = 0,009 только для БСВ) и в зависимости от источника стволовых клеток (костный мозг vs другие источники; = 0,03 только для ОВ). Многофакторный анализ подтвердил, что независимыми предикторами ухудшения ОВ и БСВ были возраст 18 лет и старше (= 0,02 и = 0,01 соответственно), активная стадия заболевания на момент аллоТГСК (= 0,04 и = 0,005 соответственно), СК (= 0,04 и = 0,0008 соответственно) и когда источником стволовых клеток служит не костный мозг (= 0,02 только для ОВ).

Заключение. В исследовании показано, что аномалии хромосомы 5 и/или 7 в составе СК, но не МК являются фактором высокого риска у больных ОМЛ после аллоТГСК, что требует особого терапевтического подхода.


Ключевые слова: острые миелоидные лейкозы, сложный кариотип, аномалии хромосом 5 и 7, аллогенная трансплантация гемопоэтических стволовых клеток, прогноз.

Получено: 5 марта 2016 г.

Принято в печать: 5 апреля 2016 г.

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ЛИТЕРАТУРА

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Мутации генов при острых миелоидных лейкозах

О.В. Блау

Клиника Шарите, Берлинский медицинский университет, ул. Хинденбургдамм, д. 30, Берлин, Германия, 12200

Для переписки: Ольга Владимировна Блау, д-р мед. наук, Department of Hematology, Oncology and Tumorimmunology, Charite University School of Medicine, Hindenburgdamm 30, 12200, Berlin, Germany; e-mail: olga.blau@charite.de.

Для цитирования: Блау О.В. Мутации генов при острых миелоидных лейкозах. Клиническая онкогематология. 2016;9(3):245-56.

DOI: 10.21320/2500-2139-2016-9-3-245-256


РЕФЕРАТ

Острый миелобластный лейкоз (ОМЛ) — клональное злокачественное заболевание, характеризующееся неэффективным гемопоэзом. Большинство больных ОМЛ имеют различные цитогенетические и молекулярно-генетические повреждения, которые сочетаются с определенными биологическими и клиническими особенностями заболевания. Примерно у 50–60 % больных de novo и у 80–95 % больных вторичными ОМЛ обнаруживаются хромосомные изменения. Следует отметить, что структурные цитогенетические аберрации являются наиболее частыми маркерами и встречаются примерно в 40 % случаев ОМЛ de novo. Достаточно большая группа больных с нормальным кариотипом (НК-ОМЛ), формально относящаяся к категории промежуточного риска, является крайне гетерогенной в отношении прогноза течения заболевания. В действующие прогностические классификации ОМЛ включены сегодня только некоторые мутации, характеризующиеся известным прогностическим значением, в частности NPM1, FLT3 и C/EBPa. Пациенты с NPM1, но без мутаций FLT3-ITD или с мутациями C/EBPa характеризуются благоприятным прогнозом заболевания, а с мутацией FLT3-ITD — неблагоприятным. Недавно выявлен новый класс мутаций, при которых повреждаются гены, ответственные за эпигенетические процессы регуляции генома, в частности метилирование ДНК или модификацию гистонов. Среди них наиболее изученными к настоящему времени являются мутации в генах DNMT3A, IDH1/2, TET2 и некоторых других. В целом ряде исследований показан неблагоприятный прогностический эффект мутации DNMT3A при ОМЛ. Что касается прогностического значения IDH1/2, то данный вопрос еще не до конца ясен. На прогноз заболевания влияет ряд биологических факторов, в т. ч. сочетание с цитогенетическими аберрациями и другими мутациями, особенно FLT3 и NPM1. Число исследований, посвященных генетическим мутациям при ОМЛ, постоянно растет. Накопленные к настоящему времени знания о генетических изменениях при ОМЛ подтверждают их роль в возникновении и развитии заболевания.


Ключевые слова: острый миелобластный лейкоз, ОМЛ, кариотип, цитогенетические аберрации, мутации генов, прогноз.

Получено: 23 января 2016 г.

Принято в печать: 4 апреля 2016 г.

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