ОБЗОРЫ

Лимфомы с первичным поражением желудка

ОБЗОРЫ , ,

А.А. Даниленко, С.В. Шахтарина, Н.А. Фалалеева

Медицинский радиологический научный центр им. А.Ф. Цыба, филиал ФГБУ «НМИЦ радиологии» Минздрава России, ул. Королева, д. 4, Калужская обл., Обнинск, Российская Федерация, 249036

Для переписки: Анатолий Александрович Даниленко, д-р мед. наук, ул. Королева, д. 4, Калужская обл., Обнинск, Российская Федерация, 249036; тел.: +7(909)250-18-10; e-mail: danilenkoanatol@mail.ru

Для цитирования: Даниленко А.А., Шахтарина С.В., Фалалеева Н.А. Лимфомы с первичным поражением желудка. Клиническая онкогематология. 2020;13(1): 95–103.

DOI: 10.21320/2500-2139-2020-13-1-95-103

РЕФЕРАТ

Лимфомы с первичным поражением желудка (ЛППЖ) встречаются чаще лимфом с вовлечением какого-либо другого органа и охватывают широкий спектр иммуноморфологических вариантов — от индолентной из клеток маргинальной зоны до агрессивной диффузной В-крупноклеточной лимфомы. ЛППЖ не имеют характерных клинических проявлений, в связи с чем в ряде случаев может быть установлен ошибочный диагноз. Вследствие редкости ЛППЖ многие связанные с ними вопросы до сих пор остаются не решенными, что нашло отражение в настоящем обзоре.

Ключевые слова: лимфомы с первичным поражением желудка, диффузная В-крупноклеточная лимфома, MALT-лимфома, Helicobacter pylori.

Получено: 29 июля 2019 г.

Принято в печать: 5 декабря 2019 г.

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Биспецифические антитела в клинике и клинических исследованиях (обзор литературы)

ОБЗОРЫ , , , ,

О.Н. Солопова, В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел. +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Солопова О.Н., Мисюрин В.А. Биспецифические антитела в клинике и клинических исследованиях (обзор литературы). Клиническая онкогематология. 2019;12(2):125–44.

DOI: 10.21320/2500-2139-2019-12-2-125-144

РЕФЕРАТ

Лечебные моноклональные антитела давно уже стали важным инструментом в руках врачей разных специальностей, прежде всего онкологов. Появление биспецифических антител открыло новые горизонты для лечения рака, стало возможным привлечение собственного иммунитета пациента к борьбе с опухолью. В данном обзоре рассматриваются все форматы и стратегии, использованные при разработке биспецифических антител, дошедших до стадии клинических исследований, а также доступные результаты этих клинических исследований.

Ключевые слова: биспецифические антитела, блинатумомаб, катумаксомаб, эмицизумаб, клиническое исследование.

Получено: 13 августа 2018 г.

Принято в печать: 22 января 2019 г.

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Клиническая эффективность хелаторной терапии у пациентов с миелодиспластическим синдромом низкого риска

ОБЗОРЫ , , , ,

С.В. Грицаев, И.И. Кострома, А.А. Жернякова

ФГБУ «Российский НИИ гематологии и трансфузиологии ФМБА», ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024

Для переписки: Сергей Васильевич Грицаев, д-р мед. наук, ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024; тел.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

Для цитирования: Грицаев С.В., Кострома И.И., Жернякова А.А. Клиническая эффективность хелаторной терапии у пациентов с миелодиспластическим синдромом низкого риска. Клиническая онкогематология. 2019;12(2):120–4.

DOI: 10.21320/2500-2139-2019-12-2-120-124

РЕФЕРАТ

В обзоре литературы представлены данные, свидетельствующие о возможности улучшения показателей крови и выживаемости у больных с миелодиспластическим синдромом низкого риска с трансфузионной зависимостью при назначении хелаторов железа. Адекватность дозы и длительность терапии — основные условия клинической эффективности хелаторов. Снижению токсических осложнений может способствовать перевод больного на прием новой формулы деферазирокса, не требующей предварительного растворения в жидкости.

Ключевые слова: миелодиспластический синдром, низкий риск, трансфузионная зависимость, хелаторы железа, выживаемость.

Получено: 20 августа 2018 г.

Принято в печать: 2 февраля 2019 г.

Читать статью в PDF 

ЛИТЕРАТУРА

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Достижения и проблемы трансплантации аллогенных гемопоэтических стволовых клеток у больных с цитогенетически неблагоприятными вариантами острых лейкозов (обзор литературы)

ОБЗОРЫ , , , , ,

Н.Н. Мамаев, Т.Л. Гиндина, Б.В. Афанасьев

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

Для переписки: Николай Николаевич Мамаев, д-р мед. наук, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: nikmamaev524@gmail.com

Для цитирования: Мамаев Н.Н., Гиндина Т.Л., Афанасьев Б.В. Достижения и проблемы трансплантации аллогенных гемопоэтических стволовых клеток у больных с цитогенетически неблагоприятными вариантами острых лейкозов (обзор литературы). Клиническая онкогематология. 2019;12(2):111–9.

DOI: 10.21320/2500-2139-2019-12-2-111-119

РЕФЕРАТ

Обзор литературы посвящен анализу результатов лечения с помощью трансплантации аллогенных гемопоэтических стволовых клеток (аллоТГСК) больных с цитогенетически неблагоприятными вариантами острых миелоидных и лимфобластных лейкозов, которые включали моносомные, сложные и гипердиплоидные кариотипы, транслокации t(3;3)/inv(3), t(v;11)(v;q23), t(4;11)(q21;q23), t(9;22)(q34;q11), аномалии abn(17p) и некоторые другие нарушения. По-видимому, основной негативный момент аллоТГСК связан с мощным повреждающим действием на хромосомы входящих в режимы кондиционирования цитостатических препаратов, что, в свою очередь, ассоциируется с появлением в опухолевых элементах дополнительных хромосомных аномалий, ростом нестабильности генома и опухолевым прогрессированием. Наоборот, одним из положительных моментов аллоТГСК может быть присущая ей реакция «трансплантат против лейкоза» (РТПЛ), степень развития которой пока изучена недостаточно. Для уменьшения риска лечения этой категории больных с помощью аллоТГСК представляется необходимым использовать новые лечебные подходы, основанные на принципах деэскалации повреждающей нагрузки на хромосомы и геном в целом, а также внедрять в клиническую практику недавно появившиеся способы активной стимуляции и качественной оценки РТПЛ.

Ключевые слова: острые лейкозы, неблагоприятные цитогенетические варианты, аллоТГСК, исходы, дополнительные хромосомные аномалии, реакция «трансплантат против лейкоза».

Получено: 22 октября 2018 г.

Принято в печать: 2 февраля 2019 г.

Читать статью в PDF 

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Актуальные вопросы канцерогенеза

ОБЗОРЫ , , , , , , , ,

И.В. Высоцкая1, В.П. Летягин2, М.А. Шабанов2, В.Ю. Кирсанов1, Е.А. Ким1, Н.В. Левкина1

1 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119991

2 ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Ирина Викторовна Высоцкая, д-р мед. наук, профессор, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119991; e-mail: vysotskaya.irina@mail.ru

Для цитирования: Высоцкая И.В., Летягин В.П., Шабанов М.А. и др. Актуальные вопросы канцерогенеза. Клиническая онкогематология. 2019;12(1):101–6.

DOI: 10.21320/2500-2139-2019-12-1-101-106

РЕФЕРАТ

В обзоре приведены современные данные об основных патогенетических механизмах, обусловливающих неконтролируемый рост и метастазирование опухоли, развитие ее резистентности к традиционным методам терапии. Генетическая нестабильность клетки, связанная с накоплением мутаций в генах контроля клеточного роста и дифференцировки, является ключевым моментом опухолевой прогрессии. Понимание и детальное изучение процессов канцерогенеза лежит в основе создания новых противоопухолевых препаратов, что, в свою очередь, позволяет оптимизировать и индивидуализировать лечение пациентов с онкологическими заболеваниями.

Ключевые слова: канцерогенез, инициация, промоция, репарация, протоонкогены, гены-супрессоры, Ras, TP53, таргетная терапия.

Получено: 27 июня 2018 г.

Принято в печать: 20 декабря 2018 г.

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Клиническое и прогностическое значение молекулярных маркеров диффузной В-крупноклеточной лимфомы

ОБЗОРЫ , , , , , ,

С.М. Расторгуев1, Д.А. Королева2, Е.С. Булыгина1, С.В. Цыганкова1, Н.Г. Гончаров1, О.С. Нарайкин1, Н.Г. Габеева2, Е.Е. Звонков2, А.В. Недолужко1

1 ФГБУ «НИЦ “Курчатовский институт”», пл. Академика Курчатова, д. 1, Москва, Российская Федерация, 123182

2 ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167

Для переписки: Артем Валерьевич Недолужко, канд. биол. наук, пл. Академика Курчатова, д. 1, Москва, Российская Федерация, 123182; тел.: +7(916)670-55-95; e-mail: nedoluzhko@gmail.com

Для цитирования: Расторгуев С.М., Королева Д.А., Булыгина Е.С. и др. Клиническое и прогностическое значение молекулярных маркеров диффузной В-крупноклеточной лимфомы. Клиническая онкогематология. 2019:12(1):95–100.

DOI: 10.21320/2500-2139-2019-12-1-95-100

РЕФЕРАТ

Диффузная В-крупноклеточная лимфома (ДВКЛ) — наиболее распространенная лимфатическая опухоль взрослых, она составляет примерно 30–40 % всех неходжкинских лимфом. К критериям диагноза относятся диффузный рост крупных анаплазированных опухолевых клеток, экспрессия В-клеточных маркеров и высокий индекс пролиферативной активности. Благодаря совершенствованию молекулярно-генетических технологий стало очевидно, что в основе клинического разнообразия лежит огромное количество генетических поломок, определяющих эпигенетическую модификацию экспрессии генов, вариабельность активации определенных сигнальных путей и иммунологические особенности опухолевых клеток. Исследование и систематизация молекулярных маркеров являются важным направлением в области диагностики и лечения ДВКЛ. В настоящем обзоре мы описываем данные о наиболее значимых молекулярных маркерах и современные представления об их клиническом значении.

Ключевые слова: лимфома, ДВКЛ, В-клетки, транскриптомика, экспрессия генов, эпигеномика, геномика.

Получено: 3 июля 2018 г.

Принято в печать: 10 декабря 2018 г.

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Роль иммунологического синапса в биологии хронического лимфолейкоза

ОБЗОРЫ , ,

Д.С. Бадмажапова, И.В. Гальцева, Е.Е. Звонков

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Дарима Сэмункоевна Бадмажапова, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(929)562-93-41; e-mail: badmazhapova-darima@mail.ru

Для цитирования: Бадмажапова Д.С., Гальцева И.В., Звонков Е.Е. Роль иммунологического синапса в биологии хронического лимфолейкоза. Клиническая онкогематология. 2018;11(4):313–8.

DOI: 10.21320/2500-2139-2018-11-4-313-318

РЕФЕРАТ

Хронический лимфолейкоз (ХЛЛ) — злокачественное лимфопролиферативное заболевание, которое проявляется накоплением опухолевых В-лимфоцитов с характерным иммунофенотипом (CD19+CD5+CD23+) в костном мозге, периферической крови и вторичных лимфоидных органах. По клиническому течению ХЛЛ является гетерогенным заболеванием. Это самый частый вид лейкоза у лиц старшей возрастной группы. Несмотря на применение новых лекарственных средств, остаются рефрактерные формы заболевания. Последние открытия в иммунологии позволили понять некоторые механизмы уклонения опухолевых клеток от иммунного надзора. Взаимодействие клеток иммунной системы друг с другом осуществляется за счет формирования иммунологического синапса, в котором основная роль отводится семейству молекул CD28/В7, так называемым иммунным контрольным точкам, регулирующим активационные и ингибирующие механизмы регуляции клеток. Приобретение клетками опухолевого фенотипа — многоступенчатый процесс, в котором клетка приобретает уникальные биологические свойства, в т. ч. и возможность быть невидимой для иммунитета. В отличие от солидных опухолей при лимфопролиферативных заболеваниях опухолевые В-лимфоциты способны экспрессировать главный комплекс гистосовместимости II класса и костимулирующие молекулы CD80 и CD86. Это свидетельствует о том, что они могут быть антигенпрезентирующими клетками для Т-клеток. Наличие коингибирующих молекул на поверхности опухолевых клеток может служить одним из факторов ингибирования иммунного ответа. В настоящем обзоре рассматриваются современные представления о биологических особенностях и иммунологических взаимодействиях клеток ХЛЛ с клетками микроокружения.

Ключевые слова: хронический лимфолейкоз, иммунологический синапс, иммунитет.

Получено: 15 марта 2018 г.

Принято в печать: 29 июня 2018 г.

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Ингибиторы иммунных контрольных точек в терапии лимфом

ОБЗОРЫ , , , , ,

К.В. Лепик

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

Для переписки: Кирилл Викторович Лепик, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: lepikkv@gmail.com

Для цитирования: Лепик К.В. Ингибиторы иммунных контрольных точек в терапии лимфом. Клиническая онкогематология. 2018;11(4):303–12.

DOI: 10.21320/2500-2139-2018-11-4-303-312

РЕФЕРАТ

Рецепторы и лиганды программируемой клеточной гибели (PD-1 и PD-L1) — наиболее изученные представители семейства иммунных контрольных точек (ИКТ), представляют собой ключевой элемент регуляции иммунного ответа. Способность злокачественных клеток воздействовать на рецепторы ИКТ является одним из важнейших механизмов подавления противоопухолевого иммунитета. Создание препаратов — ингибиторов ИКТ предоставляет возможность контроля и активации иммунного ответа, открывая новые перспективы иммунотерапии злокачественных новообразований, в т. ч. лимфом. В данном обзоре освещаются биологические основы применения ингибиторов ИКТ при классической лимфоме Ходжкина и неходжкинских лимфомах, а также представлен опыт их использования в клинике. Кроме того, обозначены новые подходы к созданию комбинированных режимов с включением ИКТ.

Ключевые слова: иммунные контрольные точки (ИКТ), PD-1, PD-L1, классическая лимфома Ходжкина, неходжкинские лимфомы, ингибиторы ИКТ.

Получено: 25 марта 2018 г.

Принято в печать: 23 июля 2018 г.

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Теория и практика иммунотерапии, направленной против антигена PRAME

ОБЗОРЫ , , , ,

В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел.: +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Мисюрин В.А. Теория и практика иммунотерапии, направленной против антигена PRAME. Клиническая онкогематология. 2018;11(2):138-49.

DOI: 10.21320/2500-2139-2018-11-2-138-149

РЕФЕРАТ

Антиген PRAME, представляющий собой значимую мишень для моноклональных антител, является онкоспецифическим маркером, который активен на всех стадиях дифференцировки опухолевых клеток, и вызывает спонтанный T-клеточный ответ. Поскольку белок PRAME экспрессируется примерно у каждого второго больного с солидными опухолями и онкогематологическими заболеваниями, иммунотерапия против данного антигена имеет значительные перспективы. В настоящем обзоре обсуждается механизм развития спонтанного иммунного ответа против PRAME и роль данного антигена в иммунном надзоре. Рассматривается процесс развития PRAME-специфических T-клеток. Оцениваются риски применения иммунотерапии против PRAME-экспрессирующей клетки. Обсуждаются достоинства и недостатки различных подходов в иммунотерапии, в т. ч. использование дендритноклеточных вакцин, вакцинирование антигеном PRAME, выведение специфических T-клеток и разработка специфических моноклональных антител. Объяснены возможные причины неудач некоторых видов иммунотерапии, представлены пути их преодоления. Поиск литературы, на которой основан данный обзор, проводился в базах данных Pubmed, Scopus и eLibrary по ключевому слову «PRAME». Рассмотрены только те публикации, в которых изучались различные аспекты или создавались средства иммунотерапии, направленной против антигена PRAME.

Ключевые слова: PRAME, иммунотерапия, дендритноклеточные вакцины, пептидные вакцины, T-клеточные вакцины, терапевтические антитела.

Получено: 19 декабря 2017 г.

Принято в печать: 5 февраля 2018 г.

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    [Misyurin VA. Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases. Clinical oncohematology

Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях

ОБЗОРЫ , ,

В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Москва, Каширское ш., д. 24, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел. +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Мисюрин В.А. Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях. Клиническая онкогематология. 2018;11(1):26–33.

DOI: 10.21320/2500-2139-2018-11-1-26-33

РЕФЕРАТ

Хотя и активность PRAME была впервые установлена при солидных опухолях, данный ген чрезвычайно часто экспрессируется при онкогематологических заболеваниях. Ген PRAME может быть использован как надежный биомаркер наличия опухолевых клеток. Определение транскриптов PRAME используется при мониторинге минимальной остаточной болезни и диагностике молекулярного рецидива. При проведении экспериментов с PRAME-экспрессирующими линиями лейкозных клеток получены противоречивые результаты. По этой причине объяснить наблюдаемое влияние экспрессии PRAME на прогноз очень сложно. Тем не менее при хронических миелопролиферативных заболеваниях и хроническом миелоидном лейкозе активность PRAME связана с худшим прогнозом, а при острых лейкозах лимфоидной и миелоидной направленности — с лучшим. Несмотря на большой объем клинических наблюдений, при некоторых нозологических формах влияние экспрессии PRAME на прогноз остается неизвестным. В настоящем обзоре литературы широко представлены известные данные об экспрессии гена PRAME при онкогематологических заболеваниях.

Ключевые слова: PRAME, лейкозы, лимфомы, прогноз.

Получено: 14 сентября 2017 г.

Принято в печать: 2 декабря 2017 г.

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