What we should know about natural killer/T‐cell lymphomas

Xiong, Jie; Zhao, Wei‐Li

doi:10.1002/hon.2588

Cited by 20 publications

(22 citation statements)

References 51 publications

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“…Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive extranodal lymphoma of NK-cell or T-cell lineage, which is highly aggressive and heterogeneous disease, with predominance in males [1][2][3][4]. Current treatment strategies (such as the combination of chemotherapy, radiotherapy, targeted therapy) can improve the complete remission of patients, but most will ultimately relapse and progress [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Plasma circulating tumor DNA assessment reveals KMT2D as a potential poor prognostic factor in extranodal NK/T-cell lymphoma

Zhang

et al. 2020

Biomark Res

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Background: The early detection of tumors upon initial diagnosis or during routine surveillance is important for improving survival outcomes. Here, we investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL). Methods: The plasma ctDNA assessment was based on blood specimens collected from 65 newly diagnosed patients with ENKTL in the hematology medical center of Xinqiao Hospital. Longitudinal samples collected under chemotherapy were also included. The gene mutation spectrum of ENKTL was analyzed via next generation sequencing. Results: We found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%) and NOTCH1 (7.7%). The mutation allele frequencies of ATM and JAK3 were significantly correlated with the disease stage, and mutated KMT2D, ASXL3 and JAK3 were positively correlated with the metabolic tumor burden of the patients. Compared with the tumor tissue, ctDNA profiling showed good concordance (93.75%). Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequencies of the genes. Compared with PET/CT, ctDNA has more advantages in tracking residual disease in patients. In addition, patients with mutated KMT2D had higher expression compared with those with wild type, and mutated KMT2D predicted poor prognosis. Conclusion: Our results unveil the mutation spectrum of ENKTL patients' plasma, which can be used to monitor the disease status of the patients exactly, and KMT2D is the most frequently mutated gene with prognosis prediction value. The application of ctDNA sequencing can provide precision treatment strategies for patients. Trial registration: This study is registered with chictr.org (ChiCTR1800014813, registered 7 February, 2018-Retrospectively registered).

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Section: Introductionmentioning

confidence: 99%

Plasma circulating tumor DNA assessment reveals KMT2D as a potential poor prognostic factor in extranodal NK/T-cell lymphoma

Zhang

et al. 2020

Biomark Res

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“…A chave para o diagnóstico do linfoma de células T/NK, além de sua característica histológica, é a demonstração de marcadores celulares T/NK, tais como CD2+, CD3 citoplasmático +, CD56 +, grânulos citotóxicos (perforina, antígeno intracelular de célula T 1, TIA1 e granzima B) e o reconhecimento do vírus EBV. Na maioria dos casos, o vírus EBV é identificado pela hibridização in situ, visto que há evidência da associação da infecção pelo vírus EBV com a patogênese da doença 3,6 . Estudos reconhecem a proteína de membrana latente 1 (LMP1) do EBV como uma oncoproteína, que leva à ativação da via de sinalização NF-κB e PI3K-AKT, a qual torna-se constantemente fosforilada e, portanto, mais ativa, podendo mediar a ativação de diversas proteínas que regulam a sobrevida e o crescimento tumoral.…”

Section: Discussionunclassified

“…Estudos reconhecem a proteína de membrana latente 1 (LMP1) do EBV como uma oncoproteína, que leva à ativação da via de sinalização NF-κB e PI3K-AKT, a qual torna-se constantemente fosforilada e, portanto, mais ativa, podendo mediar a ativação de diversas proteínas que regulam a sobrevida e o crescimento tumoral. Junto a LMP1, a LMP2, outra proteína de membrana latente, realiza a expansão e penetração de células T específicas nos locais do tumor 3 .…”

Section: Discussionunclassified

“…Verificou-se que o gene da resistência a múltiplas drogas (MDR) e seu produto, a glicoproteína P, eram expressos em células tumorais desse linfoma, sendo essa glicoproteína responsável pela resistência ao tratamento convencional. A partir disso, regimes de quimioterapia que possuem fármacos não alterados pela presença da glicoproteína P, tais como a Ifosfamida, o Metrotexato e a L-asparaginase podem ser usados no tratamento 3,7,8 .…”

Section: Discussionunclassified

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Linfoma de células T/NK nasal com pesquisa negativa para vírus Epstein Barr: relato de caso

Santos¹,

Madia²,

Twiaschor³

et al. 2020

Blucher Medical Proceedings

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“…Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive extranodal lymphoma of NK-cell or T-cell lineage, which is highly aggressive and has heterogenicity, with predominance in males (Suzuki, 2014;Tse & Kwong, 2013;Xiong & Zhao, 2019). Current treatment strategies (such as combination chemotherapy and radiotherapy and targeted therapy) can improve the complete remission of patients, but most of them will ultimately relapse and progress (Au et al, 2009;Kwong et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Genomic profiling of plasma circulating tumor DNA reveals genetics and residual disease in extranodal NK/T-cell lymphoma

Rao

Zhang

et al. 2019

Preprint

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BackgroundExtranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive hematological malignancy with poor prognosis. Early detection of tumors at initial diagnosis or during routine surveillance is important for improving survival outcomes. Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool for monitoring disease status. Here, we investigated the feasible of ctDNA detection in ENTKL.MethodsPlasma ctDNA was assessment were based on blood specimens that were collected from 65 patients recently diagnosed with ENKTL at the hematology medical center of Xinqiao Hospital, longitudinal samples collected under chemotherapy also included. Gene mutation spectrum of ENKTL was analyzed via cancer personalized profiling sequencing (CAPP-Seq). This study is registered with ClinicalTrials.gov (ChiCTR1800014813)ResultsFrom February 2017 to September 2019, 65 patients were enrolled, we found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%), NOTCH1 (7.7%). The mutation frequencies of KMT2D was significantly higher in stage III-IV, and mutations in KMT2D, ASXL3 and JAK3 were significantly correlated with the metabolic tumor burden of the patients. Compared with tumor tissue DNA, ctDNA profiling showed good concordance. Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequency of genes. Compared with PET/CT, ctDNA has more advantages for tracking residual disease in patients. In addition, we also found that mutated KMT2D predicted poor prognosis in patients.ConclusionCollectively, our results provide evidence that ctDNA may serve as a novel precision medicine biomarker in ENKTL.

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What we should know about natural killer/T‐cell lymphomas

Cited by 20 publications

References 51 publications

Plasma circulating tumor DNA assessment reveals KMT2D as a potential poor prognostic factor in extranodal NK/T-cell lymphoma

Plasma circulating tumor DNA assessment reveals KMT2D as a potential poor prognostic factor in extranodal NK/T-cell lymphoma

Linfoma de células T/NK nasal com pesquisa negativa para vírus Epstein Barr: relato de caso

Genomic profiling of plasma circulating tumor DNA reveals genetics and residual disease in extranodal NK/T-cell lymphoma

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