BCR–ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients

Carvalho, Daniel D. De; Binato, Renata; Pereira, Welbert Oliveira; Leroy, Janine Marie Gisele; Colassanti, M D; Proto‐Siqueira, Rodrigo; Bueno-da-Silva, A. E. B.; Zago, Marco Antônio; Zanichelli, Maria Aparecida; Abdelhay, Eliana; Castro, Fabíola Attié de; Jacysyn, Jacqueline F.; Amarante-Mendes, Gustavo P.

doi:10.1038/onc.2010.409

Cited by 46 publications

(45 citation statements)

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“…[20][21][22] A phase 1 trial (NCT02011945) of dasatinib and nivolumab, a PD-1 inhibitor, is recruiting, with MMR and DMR incidence as planned outcome measures. LAAs such as WT1, PRAME, PR3, and BMI-1 in CML patients represent attractive targets for immunotherapy, [23][24][25][26][27][28][29] with efficacy demonstrated in vaccination, including dendritic cell vaccination, [30][31][32][33] and, more recently, T-cell receptor-mimic antibodies. [34][35][36] In support of these studies, we observed maximal restoration of immune recovery, as demonstrated by increased effector NK cell and T-cell immune responses, reduced PD-1 inhibitory molecule expression on CD4 1 and CD8 1 T cells, and reduced numbers of Mo-MDSC in MR 4.5 only, suggesting DMR may be the preferred threshold for future TFR studies to benefit from the improved effector immune responses.…”

Section: Discussionmentioning

confidence: 99%

CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors

Hughes

Clarson

Tang

et al. 2017

Blood

145

174

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Section: Discussionmentioning

confidence: 99%

CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors

Hughes

Clarson

Tang

et al. 2017

Blood

145

174

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“…Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a new antitumour molecule, is a type II membrane protein belonging to the TNF superfamily [3], and it is abnormally expressed in a variety of cancers (higher or lower expression than normal tissues). It has been confirmed that TRAIL down-regulation by PRAME is a general phenomenon in different types of solid tumours; De Carvalho et al [4 ]also found this phenomenon in chronic myeloid leukaemia (CML) patients. However, research on the correlation between PRAME and TRAIL gene expression in different types of leukaemia patients is relatively rare.…”

Section: Introductionmentioning

confidence: 87%

Correlation between Preferentially Expressed Antigen of Melanoma and Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand Gene Expression in Different Types of Leukaemia Patients

Zhang

Chi²,

Zhang³

et al. 2013

Acta Haematol

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Introduction: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) down-regulation by preferentially expressed antigen of melanoma (PRAME) is a general phenomenon in different types of solid tumours, but research on the correlation between PRAME and TRAIL gene expression in leukaemia patients is rare. Method: PRAME and TRAIL expression was detected in bone marrow samples from 80 newly diagnosed acute leukaemia (AL) patients and 40 chronic myeloid leukaemia (CML) patients using TaqMan-based real-time quantitative PCR methods, and a linear correlation analysis was performed on their levels of expression. A total of 15 normal bone marrow samples from individuals with non-malignant haematological diseases served as normal controls. Results: PRAME expression was higher in both AL and CML patients compared to controls (both p < 0.001). CML patients in both blast crisis (BC) and the accelerated phase (AP) had significantly higher PRAME levels than CML patients in the chronic phase (CP) (p = 0.006 and 0.0461, respectively). TRAIL expression was higher in both the acute myeloid leukaemia (AML) group and the acute lymphoblastic leukaemia (ALL) group than in the controls (p = 0.039 and 0.047, respectively). In contrast, CML patients had lower TRAIL levels than controls (p = 0.043), and TRAIL expression in CML patients in the advanced phases (BC and AP) was significantly lower than in CML-CP patients (p = 0.006). In CML patients, there was a significant inverse correlation (Spearman's R = -0.6669, p < 0.0001) between PRAME and TRAIL gene expression, while a greater significant inverse correlation was found in patients in the advanced phases (BC and AP) (R = -0.6764). In addition, no correlation was observed in AML and ALL patients. Conclusion: The simultaneous detection of PRAME and TRAIL gene expression may be helpful to monitor condition changes in leukaemia patients and evaluate therapeutic effects in clinical practice, particularly in CML patients.

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“…При ХМЛ негативную роль экспрессии PRAME можно объяснить иммуносупрессией [61] и способностью белка блокировать дифференцировку клеток путем супрессии сигнального пути ретино-евой кислоты [3]. Негативный эффект экспрессии PRAME может усугубляться снижением экспрессии TRAIL, важного активатора апоптоза [66]. Однако при рассмотрении результатов экспериментов с линией лейкозных клеток K562, полученных от больной, на-ходящейся в БК ХМЛ, значимость PRAME при ХМЛ по-кажется парадоксальной.…”

Section: парадоксальность Prameunclassified

Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases

Misyurin

2018

Клиническая онкогематология

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ОБЗОРЫКлиническое значение экспрессии гена PRAME при онкогематологических заболеваниях В.А. МисюринФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Кашир-ское ш., д. 24, Москва, Российская Федерация, 115478 РЕФЕРАТХотя активность PRAME была впервые установлена при солидных опухолях, данный ген чрезвычайно часто экс-прессируется при онкогематологических заболевани-ях. Ген PRAME может быть использован как надежный биомаркер наличия опухолевых клеток. Определение транскриптов PRAME используется при мониторинге минимальной остаточной болезни и диагностике моле-кулярного рецидива. При проведении экспериментов с PRAME-экспрессирующими линиями лейкозных клеток получены противоречивые результаты. По этой причи-не объяснить наблюдаемое влияние экспрессии PRAME на прогноз очень сложно. Тем не менее при хрониче-ских миелопролиферативных заболеваниях и хрониче-ском 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 не-которых нозологических формах влияние экспрессии PRAME на прогноз остается неизвестным. В настоящем обзоре литературы широко представлены известные данные об экспрессии гена PRAME при онкогематологи-ческих заболеваниях.Ключевые слова: PRAME, лейкозы, лимфомы, прогноз.Получено: 14 сентября 2017 г. Принято в печать: 2 декабря 2017 г. ABSTRACTAlthough the PRAME activity was fi rst discovered in solid tumors, this gene is very frequently expressed in oncohematological diseases. PRAME can be regarded as a reliable biomarker of tumor cells. Determination of PRAME transcripts is used in residual disease monitoring and molecular relapse diagnostics. Experimentation with PRAME expressing lines of leukemia cells yielded controversial results. Therefore, it is hardly possible to estimate the prognostic value of PRAME activity in oncohematological diseases. In chronic myeloproliferative disease and chronic myeloid leukemia, however, PRAME activity proves to be a predictor of negative prognosis, and on the contrary, it can be regarded as a positive prognostic factor in acute myeloid or lymphoid leukemia. Despite many clinical studies prognostic value of PRAME expression in some diseases requires further investigation. The present literature review contains the data concerning PRAME expression in oncohematological diseases.

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BCR–ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients

Cited by 46 publications

References 49 publications

CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors

CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors

Correlation between Preferentially Expressed Antigen of Melanoma and Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand Gene Expression in Different Types of Leukaemia Patients

Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases

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