истинная полицитемия

Биология миелопролиферативных новообразований

МИЕЛОИДНЫЕ ОПУХОЛИ , , , , , , ,

А.Л. Меликян, И.Н. Суборцева

ФГБУ «Гематологический научный центр» Минздрава России, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167

Для переписки: Ирина Николаевна Суборцева, канд. мед. наук, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167; тел.: +7(495)612-44-71; e-mail: soubortseva@yandex.ru

Для цитирования: Меликян А.Л., Суборцева И.Н. Биология миелопролиферативных новообразований. Клиническая онкогематология. 2016;9(3):314-25.

DOI: 10.21320/2500-2139-2016-9-3-314-325

РЕФЕРАТ

Хронические миелопролиферативные заболевания (ВОЗ, 2001), или миелопролиферативные новообразования/опухоли (МПН) (ВОЗ, 2008), являются клональными заболеваниями, характеризуются пролиферацией одной или более клеточной линии миелопоэза в костном мозге с признаками сохраняющейся терминальной дифференцировки и, как правило, сопровождаются изменениями показателей крови. В группу классических Ph-негативных МПН отнесены истинная полицитемия, эссенциальная тромбоцитемия, первичный миелофиброз и МПН неклассифицируемое. Приобретенные соматические мутации, лежащие в основе патогенеза Ph-негативных МПН, представлены мутациями генов JAK2 (V617F, экзон 12), MPL, CALR. Мутации перечисленных генов наблюдаются примерно у 90 % больных. Однако данные молекулярные события не являются уникальными в патогенезе заболеваний. Мутации других генов (ТЕТ2, ASXL1, CBL, IDH1/IDH2, IKZF1, DNMT3A, SOCS, EZH2, TP53, RUNX1 и HMGA2) принимают участие в формировании фенотипа заболевания. В настоящем обзоре описываются современные представления о молекулярной биологии МПН.

Ключевые слова: хронические миелопролиферативные заболевания, миелопролиферативные новообразования, истинная полицитемия, эссенциальная тромбоцитемия, первичный миелофиброз, ген JAK2, ген CALR, ген MPL.

Получено: 11 апреля 2016 г.

Принято в печать: 11 апреля 2016 г.

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Истинная полицитемия: новая концепция диагностики и клинические формы

ОБЗОРЫ , , ,

А.М. Ковригина1, В.В. Байков2

1 ФГБУ «Гематологический научный центр» Минздрава России, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167

2 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. Рентгена, д. 12, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Алла Михайловна Ковригина, д-р биол. наук, профессор, Новый Зыковский пр-д., д. 4а, Москва, Российская Федерация, 125167; тел.: +7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

Для цитирования: Ковригина А.М., Байков В.В. Истинная полицитемия: новая концепция диагностики и клинические формы. Клиническая онкогематология. 2016;9(2):115–22.

DOI: 10.21320/2500-2139-2016-9-2-115-122

РЕФЕРАТ

Истинная полицитемия (ИП) — клональное Ph-негативное миелопролиферативное заболевание с избыточной пролиферацией 3 ростков кроветворения и исходом в стадию неэффективного миелопоэза. В классификации ВОЗ (2008) показатели гемоглобина и гематокрита включены в главные критерии диагностики заболевания. Однако у многих пациентов с ИП уровень этих показателей может оказаться ниже диагностического, что приводит к гиподиагностике данного заболевания. В настоящее время выделены три клинических формы болезни: 1) маскированная (латентная/продромальная), 2) классическая (развернутая), 3) ИП с прогрессированием/трансформацией в миелофиброз. Маскированная ИП наиболее сложна для диагностики. Она гетерогенна по клинико-лабораторным данным, анамнезу, течению заболевания; включает в себя ранние стадии, в т. ч. с высоким тромбоцитозом, имитирующие эссенциальную тромбоцитемию, случаи с абдоминальными тромбозами, а также длительно латентно протекающую ИП. Наиболее информативным способом диагностики маскированной формы ИП является исследование трепанобиоптата костного мозга. Обычно выявляется классическая картина ИП: гиперклеточный костный мозг с трехростковой пролиферацией миелопоэза, пролиферация мегакариоцитов со слабой или умеренно выраженной атипией и полиморфизмом клеток. Определение степени ретикулинового фиброза имеет важное прогностическое значение и отражает риск прогрессии/трансформации в миелофиброз. В новой редакции классификации ВОЗ (2016) морфологическое исследование трепанобиоптата костного мозга будет введено в большие критерии диагностики ИП в качестве обязательного при пограничных значениях уровня гемоглобина и гематокрита.

Ключевые слова: истинная полицитемия, миелопролиферативное заболевание, диагностика истинной полицитемии, формы истинной полицитемии.

Получено: 19 января 2016 г.

Принято в печать: 1 февраля 2016 г.

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Истинная полицитемия: обзор литературы и собственные данные

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ МИЕЛОИДНЫХ ОПУХОЛЕЙ , , ,

И.Н. Суборцева, Т.И. Колошейнова, Е.И. Пустовая, Е.К. Егорова, А.М. Ковригина, Ю.В. Плискунова, Т.В. Макарик, А.О. Абдуллаев, А.Л. Меликян

ФГБУ «Гематологический научный центр» Минздрава России, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167

Для переписки: Ирина Николаевна Суборцева, канд. мед. наук, Новый Зыковский пр-д, д. 4а, Москва, Российская Федерация, 125167; тел.: +7(495)612-44-72; e-mail: soubortseva@yandex.ru

Для цитирования: Суборцева И.Н., Колошейнова Т.И., Пустовая Е.И. и др. Истинная полицитемия: обзор литературы и собственные данные. Клиническая онкогематология. 2015;8(4):397–412.

DOI: 10.21320/2500-2139-2015-8-4-397-412

РЕФЕРАТ

Актуальность и цели. Истинная полицитемия (ИП) относится к группе классических Ph-негативных миелопролиферативных заболеваний и характеризуется панмиелозом, панцитозом, высоким риском тромбогеморрагических осложнений, низким качеством жизни из-за присутствия симптомов опухолевой пролиферации. Малые дозы ацетилсалициловой кислоты и проведение кровопусканий/эритроцитафереза рекомендованы для пациентов с низким риском тромбогеморрагических осложнений. Циторедуктивная терапия (гидроксимочевина или интерферон-a) показана пациентам с высоким риском тромбогеморрагических осложнений. В настоящее время проблемам диагностики и лечения больных ИП уделяется все большее внимание.

Методы. В статье представлены краткое описание данного заболевания, обзор современных методов лечения, результаты наблюдения за 100 больными ИП, которые получали терапию в поликлиническом отделении Гематологического научного центра. Длительность наблюдения за пациентами составила 6–262 мес. (медиана 14 мес.).

Результаты. Больные были в возрасте 23–80 лет (медиана 56 лет), доля женщин составила 67 %, мужчин — 33 %. У всех пациентов диагноз ИП установлен в соответствии с классификацией ВОЗ 2008 г. Мутация V617F гена JAK2 выявлена в 100 % наблюдений. Спленомегалия констатирована у 70 % пациентов. Плеторический синдром (гиперемия лица, ладоней, инъецированность склер) наблюдался у 65 % больных. Все пациенты предъявляли жалобы на головную боль, головокружение, а 25 % из них — на кожный зуд. Все пациенты получали симптоматическую терапию, антиагреганты, препараты, улучшающие микроциркуляцию, или антигипоксанты. Лечение проводилось в соответствии с клиническими рекомендациями: 49 % пациентов получали гидроксимочевину, 14 % — интерферон (ИФН a-2b), 14 % — комбинированную терапию (гидроксимочевину и кровопускания или ИФН a-2b и кровопускания), 23 % — только кровопускания. Ответ на лечение оценивался согласно критериям Европейской организации по изучению и лечению лейкозов 2009 г. Во всей группе больных без учета проводимой терапии частота полных ремиссий составила 48 %, частичных — 41 %, эффекта не получено у 11 % пациентов. Смена терапии осуществлялась при неэффективности, непереносимости лечения или развитии осложнений. При переключении лечения с одного метода на другой полная ремиссия не была достигнута ни у одного больного.

Заключение. Лечение ИП в основном симптоматическое. Эффективность терапии первой линии (полная ремиссия) равна 14,5–71 %. Необходимо проведение клинических исследований, направленных на оценку эффективности и безопасности новых таргетных препаратов.

Ключевые слова: миелопролиферативные заболевания, истинная полицитемия, JAK2V617F, таргетная терапия.

Получено: 30 июня 2015 г.

Принято в печать: 5 ноября 2015 г.

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