Heterogeneity of acute myeloid leukemia with the translocation t(8;21)(q22;q22)

Abstract

AIM. To characterize the clinical and hematological variability of acute myeloid leukemia (AML) with t(8;21) and to identify the signs associated with the likelihood of its relapse. MATERIALS AND METHODS. The results of examining 44 patients aged 11 to 70 years were analyzed; the efficiency of treatment was evaluated in 36. Their karyotypes were studied using the standard GTG method. Polymerase chain reaction (PCR) was employed to assess the mutational status of the FLT3, NPM1, NRAS and c-Kit genes. Qualitative PCR was used to reveal the chimeric transcript RUNX1/RUNX1T1. RESULTS. The M2 variant was verified using the French-American-British classification in 82% of cases. One patient was diagnosed with secondary AML. Additional chromosomal aberrations were found in 50% of the patients. The most common breakages were loss of one of the sex chromosomes (34.1%) and damage of chromosome 9 (16.6%). Gene mutations were detected in single cases. Following 2 7+3 induction chemotherapy (CT) cycles, complete remission (CR) was achieved in 97% of cases (3 patients with cytopenia died). Eight (25%) patients developed a relapse mainly within the first 7 months after achieving CR. The characteristic signs of relapse cases were the inefficiency of the first cycle of remission induction (RI), the absence of high-dose consolidation, damage of chromosome 9, D816V mutation in exone 17 of the c-Kit gene. Antirecurrent CT was ineffective in 5 patients. The median overall survival (OS) in patients with early recurrence was 10 months. That in the patients who were recorded to have CR was not achieved; 5-year OS was 57.8%. Chromosome 9 aberration was ascertained to have a negative impact on OS parameters (p=0.003). CONCLUSION. Patients with AML with t(8;21) is a group heterogeneous with respect to age, the morphological nature of blast cells, the pattern of the disease, the presence and type of additional chromosomal aberrations, mutations in individual genes, and clinical course. Those who are unresponsive to the first RI cycle and have additional chromosome 9 damages should be regarded as potential candidates for allogeneic hematopoietic stem cell transplantation.

Full Text

Гетерогенность острого миелоидного лейкоза с транслокацией t(8;21)(q22;q22). - Резюме. Цель исследования. Охарактеризовать клинико-гематологическую вариабельность острого миелоидного лейкоза - ОМЛ с t(8;21) и выделить признаки, сопряженные с вероятностью развития рецидива. Материалы и методы. Проанализированы результаты обследования 44 больных в возрасте от 11 до 70 лет, эффективность лечения оценена у 36. Кариотип изучен в стандартном GTG-методе. Для оценки мутационного статуса генов FLT3, NPM1, NRAS и c-Kit использован метод полимеразной цепной реакции (ПЦР). Метод качественной ПЦР применен для выявления химерного транскрипта RUNX1/RUNX1T1. Результаты. В 82% случаев верифицирован вариант М2 по классификации FAB. У 1 больного диагностирован вторичный ОМЛ. У 50% больных выявлены дополнительные хромосомные аберрации. Наиболее частые поломки - потеря одной из половых хромосом (34,1%), повреждения 9-й хромосомы (16,6%). Мутации генов обнаружены в единичных случаях. Полная ремиссия (ПР) после 2 индукционных курсов химиотерапии (ХТ) 7+3 достигнута в 97% случаев (в период цитопении умерли 3 больных). Рецидив развился у 8 (25%) больных преимущественно в первые 7 мес после достижения ПР. Характерными признаками случаев с рецидивом были неэффективность первого курса индукции ремиссии (ИР), отсутствие высокодозной консолидации, повреждения 9-й хромосомы, мутация D816V в 17-м экзоне гена c-Kit. Противорецидивная ХТ была неэффективной у 5 больных. Медиана общей продолжительности жизни больных с ранним рецидивом составила 10 мес. Медиана ОВ больных, у которых зарегистрирована ПР, не достигнута, 5-летняя ОВ составила 57,8%. Обнаружено негативное влияние аберрации 9-й хромосомы на показатели ОВ (р=0,003). Заключение. Больные ОМЛ с t(8;21) - гетерогенная группа по возрасту, морфологической природе бластных клеток, характеру болезни, наличию и виду дополнительных хромосомных аберраций, мутациям отдельных генов и клиническому течению. Больных без ответа на первый курс ИР и с дополнительными повреждениями 9-й хромосомы следует рассматривать как потенциальных кандидатов на трансплантацию аллогенных гемопоэтических стволовых клеток.
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Copyright (c) 2014 Gritsaev S.V., Martynkevich I.S., Ziuzgin I.S., Kariagina E.V., Martynenko L.S., Petrova E.V., Tsybakova N.I., Ivanova M.P., Kostroma I.I., Tiranova S.A., Potikhonova N.A., Abdulkadyrov K.M.

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