bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2021-66-1-54-67bloodjour-271Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСтруктура и значение цитогенетических перестроек у больных множественной миеломойStructure and signifi cance of cytogenetic abnormalities in patients with multiple myelomahttps://orcid.org/0000-0003-3163-4930АбрамоваТ. В.AbramovaT. V.

Абрамова Татьяна Валерьевна, кандидат медицинских наук, врач лаборатории кариологии

125167, Москва

Tatiana V. Abramova, Cand. Sci. (Med.), Physician, Laboratory of Karyology

125167, Moscow

abramova.blood@gmail.comhttps://orcid.org/0000-0003-1613-652XОбуховаТ. Н.ObukhovaT. N.

Обухова Татьяна Никифоровна, кандидат медицинских наук, заведующая лабораторией кариологии

125167, Москва

Tatiana N. Obukhova, Cand. Sci. (Med.), Head of the Laboratory of Karyology

125167, Moscow

obukhova_t@mail.ruhttps://orcid.org/0000-0002-4155-7820ГрибановаЕ. О.GribanovaE. O.

Грибанова Елена Олеговна, кандидат медицинских наук, заведующая отделением интенсивной высокодозной химиотерапии гематологических заболеваний с  круглосуточным и дневным стационарами

125167, Москва

Elena O. Gribanova, Cand. Sci. (Med.), Head of the Department of Intensive High-Dose Chemotherapy for Hematological Diseases with round-the-clock and day hospitals

125167, Moscow

gribanova.e@blood.ruhttps://orcid.org/0000-0002-7944-6202СоловьевМ. В.SolovevM. V.

Соловьев Максим Валерьевич, кандидат медицинских наук, заведующий отделением интенсивной высокодозной химиотерапии парапротеинемических гемобластозов

125167, Москва

Maxim V. Solovev, Cand. Sci. (Med.), Head of the Department of Intensive High-Dose Chemotherapy for Paraproteinemic Hemoblastosis

125167, Moscow

maxsolovej@mail.ruhttps://orcid.org/0000-0003-4142-171XФирсоваМ. В.FirsovaM. V.

Фирсова Майя Валерьевна, кандидат медицинских наук, старший научный сотрудник отделения высокодозной химиотерапии парапротеинемических гемобластозов

125167, Москва

Maiia V. Firsova, Cand. Sci. (Med.), Senior Researcher, Department of Intensive High-Dose Chemotherapy for Paraproteinemic Hemoblastosis

125167, Moscow

firs-maia@yandex.ruВотяковаО. М.VotyakovaO. M.

Вотякова Ольга Михайловна, кандидат медицинских наук, старший научный сотрудник отделения химиотерапии гемобластозов

115478, Москва

Olga M. Votyakova, Cand. Sci. (Med.), Senior Researcher, Department of Chemotherapy for Hemoblastosis

115478, Moscow

omvtk@yandex.ruhttps://orcid.org/0000-0002-6288-7570КуликовС. М.KulikovS. M.

Куликов Сергей Михайлович, кандидат технических наук, заведующий информационно-аналитическим отделом

125167, Москва

Sergey M. Kulikov, Cand. Sci. (Tech.), Head of the Information and Analytical Department

125167, Moscow

smkulikov@mail.ruhttps://orcid.org/0000-0001-8044-598XЧабаеваЮ. А.ChabaevaYu. A.

Чабаева Юлия Александровна, кандидат технических наук, старший научный сотрудник информационно-аналитического отдела

125167, Москва

Yulia A. Chabaeva, Cand. Sci. (Tech.), Senior Researcher, Information and Analytical Department

125167, Moscow

uchabaeva@gmail.comhttps://orcid.org/0000-0002-8490-6066ГальцеваИ. В.Gal’tsevaI. V.

Гальцева Ирина Владимировна, кандидат медицинских наук, заведующая лабораторией иммунофенотипирования клеток крови и костного мозга

125167, Москва

Irina V. Gal’tseva, Cand. Sci. (Med.), Head of the Laboratory of Blood and Bone Marrow Immunophenotyping

125167, Moscow

irinagaltseva@gmail.comhttps://orcid.org/0000-0002-4966-8146МенделееваЛ. П.MendeleevaL. P.

Менделеева Лариса Павловна, доктор медицинских наук, профессор, руководитель управления по научной и образовательной работе, заведующая отделом химиотерапии парапротеинемических гемобластозов

125167, Москва

Larisa P. Mendeleeva, Dr. Sci. (Med.), Professor, Director of the Science and Education Office, Head of the Department of Chemotherapy for Paraproteinemic Hemoblastosis

125167, Moscow

mendeleeva.L@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Министерства здравоохранения Российской ФедерацииРоссияN.N. Blokhin National Medical Research Center of OncologyRussian Federation2021180520216615467Copyright © Абрамова Т.В., Обухова Т.Н., Грибанова Е.О., Соловьев М.В., Фирсова М.В., Вотякова О.М., Куликов С.М., Чабаева Ю.А., Гальцева И.В., Менделеева Л.П., 20212021Абрамова Т.В., Обухова Т.Н., Грибанова Е.О., Соловьев М.В., Фирсова М.В., Вотякова О.М., Куликов С.М., Чабаева Ю.А., Гальцева И.В., Менделеева Л.П.Abramova T.V., Obukhova T.N., Gribanova E.O., Solovev M.V., Firsova M.V., Votyakova O.M., Kulikov S.M., Chabaeva Y.A., Gal’tseva I.V., Mendeleeva L.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/271Введение

Введение. Цитогенетические и  молекулярно-генетические особенности опухолевых клеток считают наиболее важными факторами, определяющими течение множественной миеломы (ММ). Отдельные хромосомные аномалии имеют прогностическое значение при ММ и определяют ответ на терапию и выживаемость больных.

Цель — определить спектр и частоту встречаемости хромосомных нарушений у больных ММ и их связь с клиническим течением заболевания.

Материалы и методы

Материалы и методы. В исследование включено 134 больных ММ, у которых до начала лечения исследовали хромосомные нарушения с помощью флуоресцентной гибридизации in situ (fl uorescence in situ hybridization — FISH) костного мозга с ДНК-зондами для выявления t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), гипердиплоидии, del13q14/-13, del17p13/TP53, amp1q21, t(8q24)/сMYC. В дебюте ММ исследовали гемограмму, активность лактатдегидрогеназы (ЛДГ), концентрации кальция, β2-микроглобулина, креатинина, выполняли цитологическое исследование пунктата, гистологическое исследование трепанобиоптата костного мозга и/или биоптата мягкотканного образования, рентгеновское исследование костей, оценивали иммунохимический вариант ММ, стадию заболевания. Медиана наблюдения за больными составила 20 месяцев (3,2–77,4).

Результаты

Результаты. Частота первичных хромосомных нарушений составила 82,9 %, среди них t(14q32)/IGH — 29,1 %, множественные трисомии  — 46,3  %, их сочетание  — 7,5  %. Частота встречаемости отдельных t(14q32)/IGH) составила: t(11;14) — 16,4 %, t(4;14) — 12,7 %, t(14;16) и t(14;20) — 3,7 и 2,2 % соответственно. Частота вторичных хромосомных нарушений составила 69,4 %, среди них del13q14/-13 — 40,3 %, amp1q21 — 39,6 %, t(8q24)/сMYC — 17,2 %, del17р13/TP53 — 12,7 %, del1p32 — 2,2 %. Анализ сочетания первичных и вторичных хромосомных нарушений показал, что del13q14/-13 чаще выявлялась в сочетании с t(4;14) и реже — с множественными трисомиями (р<0,05). Amp1q21 чаще обнаружена одновременно с t(4;14) и реже — с t(11;14) (р <0,05) диагностировали анемию с концентрацией гемоглобина менее 100 г/л, а при наличии amp1q21 и del17p13/TP53 — повышенную активность ЛДГ в  сыворотке крови (р<0,05). T(8q24)/cMYC чаще сопровождались повышенной концентрацией β2-микроглобулина в сыворотке крови (р < 0,05). Трехлетняя общая выживаемость (ОВ) в группах больных с del17p13/TP53 составила 35,5 % против 71,3 % без нее (р = 0,002), в группах больных с t(8q24)/cMYC — 50,8 % против 67 % без нее (р = 0,001). У больных без amp1q21, с одной дополнительной копией 1q21 или с двумя и более дополнительными копиями 1q21 пятилетняя ОВ составила 79,4, 67,3 и 20,9 % соответственно (р = 0,0016), а двухлетняя выживаемость без прогрессии (ВБП) — 83, 50 и 0 % соответственно (р = 0,005).

Заключение

Заключение. Установлено негативное влияние del17p13/TP53 и  t(8q24)/cMYC на ОВ больных ММ, а  также неблагоприятное влияние аmp1q21 при наличии двух и более дополнительных копий локуса 1q21 на ОВ и ВБП.

Introduction

Introduction. Cytogenetic and genomic traits of tumour cells are considered the key mediating factors in multiple myeloma (MM). Selected chromosomal abnormalities are prognostic of therapeutic response and patient survival in MM.

Aim — to assess of the diversity and rate of chromosomal abnormalities in MM patients and their association with the disease course.

Materials and methods

Materials and methods. The study enrolled 134 MM patients with pre-treatment bone marrow FISH assay screening for chromosomal abnormalities: t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), hyperdiploidy, del13q14/-13, del17p13/TP53, amp1q21, t(8q24)/cMYC. The studied criteria at the MM onset were: hemogram, lactate dehydrogenase (LDH) activity, calcium, β2-microglobulin and creatinine concentrations, punctate cytology, bone marrow trephine biopsy and/or soft tissue biopsy histology, bone X-ray, immunochemical variant of MM, disease staging. A median follow-up was 20 months (3.2–77.4).

Results

Results. The primary chromosomal abnormality rate was 82.9  %, among them t(14q32)/IGH  — 29.1  %, multiple trisomies — 46.3 % and their combination — 7.5 %. The rates of particular t(14q32)/IGH): t(11;14) — 16.4 %, t(4;14) — 12.7 %, t(14;16) and t(14;20) — 3.7 and 2.2 %, respectively. The secondary chromosomal abnormality rate was 69.4 %, among them del13q14/-13 — 40.3 %, amp1q21 — 39.6 %, t(8q24)/cMYC — 17.2 %, del17p13/TP53 — 12.7 %, del1p32 — 2.2 %. Analyses of the primary–secondary abnormality combinations showed that del13q14/-13 is more frequently combined with t(4;14) and less frequently with trisomies (p < 0.05). Amp1q21 occurs more frequently with t(4;14) and less — with t(11;14) (p<0.05). Patients with t(4;14) more frequently (p < 0.05) had anemia at a hemoglobin level<100 g/L, and the presence of amp1q21 and del17p13/TP53-enhanced serum LDH activity (p < 0.05). Abnormality t(8q24)/cMYC more often co-occurred with higher serum β2-microglobulin concentrations (p < 0.05). A three-year overall survival (OS) in del17p13/TP53-positive patients was 35.5 vs. 71.3 % in the negative (p = 0.002) and 50.8 vs. 67 % — in t(8q24)/cMYC-positive and negative patients, respectively (p = 0.001). Patients without amp1q21, with one, with two or more additional 1q21 copies had a five-year OS 79.4, 67.3 and 20.9 %, respectively (p = 0.0016), and a two-year progression-free survival (PFS) 83, 50 and 0 %, respectively (p = 0.005).

Conclusion

Conclusion. We establish a negative impact of del17p13/TP53 and t(8q24)/cMYC on patients’ OS in MM, as well as unfavourable effect of amp1q21 on OS and PFS in the presence of two or more additional copies of 1q21 loci.

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The authors declare that there are no conflicts of interest present.