BRAF and MAP2K1 mutations in hairy cell leukemia and splenic marginal zone B-cell lymphoma

Якутик, И А; Аль-Ради, Р. С.; Джулакян, У. Л.; Бидерман, Б В; Sudarikov, Andrey

doi:10.17650/1818-8346-2016-11-1-34-36

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Мутации в экзонах 11 и 15 гена BRAF и в экзонах 2, 3 и 11 гена MAP2K1 исследовали методом прямого сек-венирования по Сэнгеру в соответствии с методикой, описанной ранее [13].…”

Section: материалы и методыunclassified

Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Kovrigina¹,

Korzhova²,

Аль-Ради³

et al. 2016

Клиническая онкогематология

View full text Add to dashboard Cite

РЕФЕРАТАктуальность. В-клеточная лимфома селезенки неклас-сифицируемая -редкая и малоизученная нозологическая форма, впервые введенная в классификацию опухолей кро-ветворной и лимфоидной тканей ВОЗ в 2008 г. Эта форма лимфомы предполагает проведение дифференциальной диагностики между вариантным волосатоклеточным лей-козом (ВКЛ) и диффузной мелкоклеточной В-клеточной лимфомой красной пульпы селезенки (ДЛКПС). Цель. Разработать критерии диагностики ДЛКПС путем сопоставления трепанобиоптатов костного мозга и опера-ционного материала селезенки. Методы. В патологоанатомическом отделении ГНЦ МЗ РФ проведено сопоставление трепанобиоптатов костного моз-га и операционного материала селезенки (2013-2015 гг.) у 71 пациента (мужчины/женщины 1:2,6, возрастной диапазон 44-81 год, медиана 58 лет) с использованием морфологи-ческого и расширенного иммуногистохимического исследо-вания. В целях анализа мутационного статуса IgHV и выяв-ления мутаций MAP2K1, NOTCH, BRAF использован метод секвенирования по Сэнгеру, а также ПЦР-исследование. У 5 пациентов на образцах операционного материала селе-зенки проведено молекулярное исследование. Результаты. У 5 (7 %) из 71 пациента установлен диагноз ДЛКПС. В двух группах пациентов (с нормальным и высо-ким числом лейкоцитов) в ткани селезенки морфологиче-ская картина была сходной с опухолевым субстратом ВКЛ. При иммуногистохимическом исследовании во всех слу-чаях отмечалась мономорфная экспрессия опухолевыми клетками CD20, DBA.44 при вариабельности экспрессии CD11c, TRAP, CD103, CD123. Ни в одном из 5 наблюдений не выявлено экспрессии CD25, CD27, Cyclin D1, Annexin-1. В костном мозге в отличие от ВКЛ и его вариантной формы отмечалась преимущественно интерстициально-внутрисо-судистая скудная CD20+ лимфоидная инфильтрация (4 из 5 случаев) без различимых ядрышек в ядрах небольших лимфоидных клеток. В 1 наблюдении лимфоидная инфиль-трация носила смешанный характер -CD20+ мелкооча-гово-интерстициальная с внутрисосудистым компонентом. [2013][2014][2015] were compared in 71 patients (men/women ratio 1:2.6, age range 44-81, median age 58 years) using morphological and extended immunohistochemical studies. Sanger sequencing and PCR assay were carried out to analyze the mutational status of IgHV and to identify mutations in MAP2K1, NOTCH, BRAF. Results. SDRPL was diagnosed in 5 (7 %) of 71 patients. In 2 groups of patients (with normal and high WBC count), the morphological features of spleen tissue were similar to those of a neoplastic substrate of HCL-V. The immunohistochemical assay demonstrates monomorphic expression of CD20 and DBA.44 and heterogeneous expression of CD11c, TRAP, CD103, CD123 in all cases. In none of the 5 cases, expression of CD25, CD27, Cyclin D1, Annexin-1 was found. In bone marrow (unlike HCL and HCL-V), predominantly interstitial and intravascular scant CD20+ lymphoid infiltration (4 of 5 cases) was found without detectable nucleoli in nuclei of small lymphoid cells. In 1 case, there was a combined lymphoid infiltration: CD20+ microfocalinterstitial infiltration with an intra...

show abstract

Section: материалы и методыunclassified

Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Kovrigina¹,

Korzhova²,

Аль-Ради³

et al. 2016

Клиническая онкогематология

View full text Add to dashboard Cite

show abstract

Expression features of antigens involved in the formation of immunological synapse in splenic marginal zone lymphoma

et al. 2020

View full text Add to dashboard Cite

Background. Splenic marginal zone lymphoma (SMZL) is an indolent non-Hodgkin’s B-cell lymphoma. It presents morphologically by mature lymphoid B-cells. They conform to these immunological characteristics of marginal zone lymphocytes from secondary follicles. The tumor B-cells of SMZL do not have specific markers of immunophenotype and requires the exclusion of other non-Hodgkin’s B-cell lymphomas. There is an annual increase in the incidence of SMZL. There are refractory forms and progressive course of the SMZL. There is a huge variety of the mechanisms of evading tumor cells from immunological control. Unlike solid tumors, B-lymphoproliferative diseases are characterized by the expression of HLA I/II and co-stimulatory molecules (CD80 and CD86). Therefore, tumor B-lymphocytes can act as antigen-presenting cells (APC) for T lymphocytes. The T-cell immune response is known to play an important role in antitumor control. It is known that effective activation of T-lymphocytes requires the formation of an immunological synapse and the presence of two activation signals (antigen recognition and co-stimulation of CD28-CD80/86). According to the modern concept of tumor development, there is a gradual selection of tumor clones. As a result, only tumor cells that are invisible to the immune system remain. Mechanisms of evasion of tumor B-cells of SMZL from immune surveillance are currently not fully understood and are being actively studied.Objective: to study the expression features of antigens involved in the formation of immunological synapse in patients with SMZL in peripheral blood.Materials and methods. The study includes 10 primary SMZL patients; all patients have stage IV according to the Ann Arbor classification. Splenectomy was performed for all patients as a first stage of treatment. Two patients had progression of SMZL after splenectomy, which required chemotherapy. The control group included 25 healthy donors. Peripheral blood was used as a material for analysis. The study was conducted on a 6-color BD FACS Canto II flow cytometer (BD Biosciences, USA) immediately after diagnosis.Results. Tumor B-cells of SMZL are different from B-cells of healthy donors with a greater proportion of CD80+, FAS+, PD-1+-cells, which may correspond to activated B-cells. The proportion of CD4+PD-1+ and CD8+PD-1+ T-cells in patients with SMZL was higher in comparison with the control group. There was a large proportion of T-cells expressing PD-1 in the group of patients with SMZL progression after splenectomy in comparison with the group of patients with indolent course of SMZL. Conclusion. Thereby, tumor B-cells of the SMZL retains the features of non-tumor analogues. The most significant mechanism for evading immune surveillance in an SMZL is inhibition of the T-cell immunity via the PD-1–PD-L1 pathway. The most pronounced inhibition of T-cell immunity causes an uncontrolled tumor process.

show abstract

BRAF and MAP2K1 mutations in hairy cell leukemia and splenic marginal zone B-cell lymphoma

Cited by 2 publications

References 10 publications

Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Expression features of antigens involved in the formation of immunological synapse in splenic marginal zone lymphoma

Contact Info

Product

Resources

About