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https://www.readbyqxmd.com/read/28691928/mutations-in-5-methylcytosine-oxidase-tet2-and-rhoa-cooperatively-disrupt-t-cell-homeostasis
#1
Shengbing Zang, Jia Li, Haiyan Yang, Hongxiang Zeng, Wei Han, Jixiang Zhang, Minjung Lee, Margie Moczygemba, Sevinj Isgandarova, Yaling Yang, Yubin Zhou, Anjana Rao, M James You, Deqiang Sun, Yun Huang
Angioimmunoblastic T cell lymphoma (AITL) represents a distinct, aggressive form of peripheral T cell lymphoma with a dismal prognosis. Recent exome sequencing in patients with AITL has revealed the frequent coexistence of somatic mutations in the Rho GTPase RhoA (RhoAG17V) and loss-of-function mutations in the 5-methylcytosine oxidase TET2. Here, we have demonstrated that TET2 loss and RhoAG17V expression in mature murine T cells cooperatively cause abnormal CD4+ T cell proliferation and differentiation by perturbing FoxO1 gene expression, phosphorylation, and subcellular localization, an abnormality that is also detected in human primary AITL tumor samples...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28634614/detection-of-the-circulating-tumor-dnas-in-angioimmunoblastic-t-cell-lymphoma
#2
Mamiko Sakata-Yanagimoto, Rie Nakamoto-Matsubara, Daisuke Komori, Tran B Nguyen, Keiichiro Hattori, Toru Nanmoku, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa, Atsushi Shinagawa, Shigeru Chiba
Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis...
June 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28622960/treatment-of-peripheral-t-cell-lymphoma-in-community-settings
#3
Tatyana Feldman, Charles M Farber, Kelly Choi, Claudio Faria, Andre Goy, Jacqueline Connors, Dhakshila Paramanathan, Sukhi Kaur, Eric Schultz, Michael McGuire, Stuart L Goldberg
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) represent a rare and heterogeneous group of malignancies that do not have consensus treatment recommendations. Strategies extrapolated from B-cell lymphoma have met with limited efficacy, although T-cell-specific salvage therapies have been recently developed. METHODS: To determine treatment patterns and associated outcomes in PTCL not otherwise specified (PTCL-NOS), anaplastic large T-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL), a retrospective analysis was undertaken at a large US community oncology network among patients treated between January 2010 and April 2015...
June 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28543514/angioimmunoblastic-t-cell-lymphoma-more-than-a-disease-of-t-follicular-helper-cells
#4
François Lemonnier, Tak W Mak
Angioimmunoblastic T cell lymphoma (AITL) is one of the most frequent entities of peripheral T cell lymphoma. An AITL has two components: the AITL tumor cells that have a T follicular helper (TFH) cell phenotype, and a surrounding and extensive tumor microenvironment that is populated with various reactive cell types, including B cells. Recurrent TET2 mutations have been described in 50-80% of AITLs, possibly occurring in a hematopoietic progenitor cell. An article published recently in The Journal of Pathology describes the use of microdissection to isolate PD1(+) AITL tumor cells and CD20(+) B cells from the AITL microenvironment and to show that TET2 mutations are actually more frequent in these diseases than previously thought...
May 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28529614/irf4-mum1-expression-is-associated-with-poor-survival-outcomes-in-patients-with-peripheral-t-cell-lymphoma
#5
Mi Hwa Heo, Ha Young Park, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Background: Interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) is a member of the interferon regulatory factor family of transcriptional factors. Although IRF4/MUM1 expression is associated with aggressiveness of B-cell lymphoma and multiple myeloma, the prognostic value of IRF4/MUM1 expression in peripheral T-cell lymphoma (PTCL) is unclear. Methods: We analyzed a tissue array from 69 patients diagnosed with PTCL. The expression levels of IRF4/MUM1 and associated proteins such as MYC and Ikaros were analyzed by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28505169/molecular-basis-of-targeted-therapy-in-t-nk-cell-lymphoma-leukemia-a-comprehensive-genomic-and-immunohistochemical-analysis-of-a-panel-of-33-cell-lines
#6
Rufino Mondejar, Cristina Pérez, Arantza Onaindia, Nerea Martinez, Julia González-Rincón, Helena Pisonero, Jose Pedro Vaqué, Laura Cereceda, Miguel Santibañez, Margarita Sánchez-Beato, Miguel Angel Piris
T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28487786/a-rare-case-of-angioimmunoblastic-t-cell-lymphoma-with-epstein-barr-virus-negative-reed-sternberg-like-b-cells-chylous-ascites-and-chylothorax
#7
Mathijs Willemsen, Arne W J H Dielis, Iryna V Samarska, Ad Koster, Arienne M van Marion
Angioimmunoblastic T-cell lymphoma is a rare non-Hodgkin lymphoma with dismal prognosis. The median age of presentation ranges from 62 to 69 years with generalized lymphadenopathy, B symptoms, and hepatosplenomegaly as the most prevalent symptoms. The combination of B-cell and T-cell proliferations is common in AITL and the B-cell component may resemble Reed-Sternberg-like B-cells. Epstein-Barr virus is estimated to be present in 80-95% of AITL biopsies. Only a handful of EBV-negative AITL cases with EBV-negative RS-like B-cells have been reported over the last decade...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28481741/cardiac-tamponade-as-initial-presentation-of-angioimmunoblastic-t-cell-lymphoma
#8
Xu Zhang, Ji Chao Zhang, Rong Xing Liu, Qi Miao
A 21-year-old man presented initially with impending cardiac tamponade secondary to an angioimmunoblastic T-cell lymphoma (AITL). Following unsuccessful pericardiocentesis and subxiphoid pericardiostomy, the patient's deteriorating hemodynamics prompted an urgent sternotomy. Histopathological diagnosis confirmed AITL. While chemotherapy remains the most effective treatment of AITL, life-threatening complications of the tumor necessitates surgical intervention.
March 6, 2017: Heart Surgery Forum
https://www.readbyqxmd.com/read/28337768/tet2-mutations-in-b-cells-of-patients-affected-by-angioimmunoblastic-t-cell-lymphoma
#9
Friederike H Schwartz, Qian Cai, Eva Fellmann, Sylvia Hartmann, Mikko I Mäyränpää, Marja-Liisa Karjalainen-Lindsberg, Christer Sundström, René Scholtysik, Martin-Leo Hansmann, Ralf Küppers
Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1(+) cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated...
June 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28306367/the-clinical-significance-of-epstein-barr-virus-dna-in-peripheral-blood-mononuclear-cells-in-patients-with-non-hodgkin-lymphoma
#10
Yi Chen, Xiaoyun Zheng, Buyuan Chen, Xiaozhu Yang, Jing Zheng, Zhihong Zheng, Ting Yang, Tingbo Liu, Jianda Hu
The aim of the study was to determine the clinical significance of EBV DNA in the peripheral blood mononuclear cells (PBMCs) from the patients with non-Hodgkin lymphoma (NHL). Newly diagnosed patients with NHL were enrolled in the study (n = 328), and clinical data retrospectively analyzed. EBV DNA was detectable in 34.8% of patients, and the positivity rate was 51.6% for T/NK cell subtype and 24.3% for B cell subtype (p < .001). In diffuse large B cell lymphoma (DLBCL), extranodal NK/T-cell lymphoma, nasal type (ENKTL), peripheral T-cell lymphoma not otherwise classified (PTCL...
March 17, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28209473/analysis-of-peripheral-t-cell-lymphoma-diagnostic-workup-in-the-united-states
#11
Eric D Hsi, Steven M Horwitz, Kenneth R Carson, Lauren C Pinter-Brown, Steven T Rosen, Barbara Pro, Massimo Federico, Christian Gisselbrecht, Marc Schwartz, Lisa A Bellm, Mark Acosta, Angela M Collie, Aaron M Gruver, Bartosz J Grzywacz, Samir Turakhia, Andrei R Shustov, Ranjana H Advani, Tatyana Feldman, Mary Jo Lechowicz, Sonali M Smith, Frederick Lansigan, Anil Tulpule, Michael D Craig, John P Greer, Brad S Kahl, Joseph W Leach, Neil Morganstein, Carla Casulo, Steven I Park, Francine M Foss
BACKGROUND: With increased understanding of the unique entities, subtype-specific approaches for peripheral T-cell lymphoma (PTCL) are emerging, and more precise diagnoses are becoming increasingly important. PATIENTS AND METHODS: We analyzed the approach to the histopathologic diagnosis of PTCL using data from the comprehensive oncology measures of peripheral T-cell lymphoma (COMPLETE) study. The COMPLETE trial is a large prospective cohort study of patients with newly diagnosed PTCL in the United States...
January 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28194275/inappropriate-costimulation-and-aberrant-dna-methylation-as-therapeutic-targets-in-angioimmunoblastic-t-cell-lymphoma
#12
EDITORIAL
Mathijs Willemsen, Harry C Schouten
Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of peripheral T-cell lymphoma. Advances in understanding the mutational landscape of AITL have not resulted in improved prognosis nor consensus regarding optimal first-line and second-line treatment. The recently proposed multistep tumorigenesis model for AITL provides a theoretical framework of AITL oncogenesis. In this model, early mutations in epigenetic modifiers interact with late cooperative mutations to enable malignant transformation...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28188140/angioimmunoblastic-t-cell-lymphoma-with-polyarthritis-resembling-rheumatoid-arthritis
#13
Ralph Yachoui, Nouman Farooq, Jonathan V Amos, Gene R Shaw
Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL). AITL typically presents with lymphadenopathy, fever, rash, hepatosplenomegaly, and rarely polyarthritis. We report the case of a 50-year-old female who presented with lymphadenopathy, rash, and symmetric polyarthritis. She was later diagnosed with AITL and was treated with chemotherapy with resolution of arthritis. AITL should be suspected in paitents presenting with rheumatoid-like arthritis and diffuse lymphadenopathy...
December 2016: Clinical Medicine & Research
https://www.readbyqxmd.com/read/28148900/angioimmunoblastic-t-cell-lymphoma-novel-molecular-insights-by-mutation-profiling
#14
Ming Wang, Shaowei Zhang, Shih-Sung Chuang, Margaret Ashton-Key, Eguzkine Ochoa, Niccolo Bolli, George Vassiliou, Zifen Gao, Ming-Qing Du
Angioimmunoblastic T cell lymphoma (AITL) originates from follicular helper T-cells and is characterised by a polymorphic infiltrate with the neoplastic T-cells forming small clusters around the follicle and high endothelial venules. Despite the recent advances in its phenotypic characterisation, the genetics and molecular mechanisms underlying AITL are not fully understood. In the present study, we performed whole exome sequencing in 9 cases of AITL from Taiwan (n = 6) and U.K. (n = 3). We confirmed frequent mutations in TET2 (9/9), DNMT3A (3/9), IDH2 (3/9), RHOA (3/9) and PLCG1 (2/9) as recently reported by others...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115369/angioimmunoblastic-t-cell-lymphoma-the-many-faced-lymphoma
#15
REVIEW
Matthew A Lunning, Julie M Vose
Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the literature would suggest given the many names that have preceded it. Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28053548/recombinant-human-endostatin-in-combination-with-chop-regimen-for-peripheral-t-cell-lymphoma
#16
Qunling Zhang, Junning Cao, Kai Xue, Xiaojian Liu, Dongmei Ji, Ye Guo, Xiaonan Hong
Peripheral T cell lymphoma (PTCL) has a poor prognosis. Overexpression of vascular endothelial growth factor (VEGF) might contribute to the poor prognosis of PTCL and could be the target of novel therapy. The efficacy and safety of recombinant human endostatin (Endostar) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (ECHOP) have been explored in 15 PTCL patients. The objective response rate was 80%, with 53.3% patients having achieved complete response (CR) rate. The CR rate was 100% (3/3) in angioimmunoblastic T cell lymphoma (AITL) patients compared to only 36...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28050005/angioimmunoblastic-t-cell-lymphoma-associated-with-iga-nephropathy
#17
Yukinori Harada, Kei Sakai, Shiho Asaka, Kazutaka Nakayama
Few cases of IgA nephropathy with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We herein present the case of a 79-year-old Japanese man with AITL and IgA nephropathy. The patient presented with generalized edema, fatigue, and fever. Laboratory investigations revealed polyclonal gammopathy with a high level of IgA, microscopic hematuria, proteinuria, and some other immunological abnormalities. Computed tomography revealed generalized lymphadenopathy. A diagnosis of AITL and IgA nephropathy was made based on inguinal lymph node and renal biopsies...
2017: Internal Medicine
https://www.readbyqxmd.com/read/27995879/-comparison-of-allogeneic-or-autologous-hematopoietic-stem-cell-transplant-for-high-risk-peripheral-t-cell-lymphomas
#18
Q L Wang, H W Huang, Z M Jin, X W Tang, H Y Qiu, C C Fu, Y Han, M Miao, H R Chang, A N Sun, D P Wu
Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (12-58) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 angioimmunoblastic T-cell lymphoma (AITL)...
November 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27983760/the-survival-outcome-of-patients-with-relapsed-refractory-peripheral-t-cell-lymphoma-not-otherwise-specified-and-angioimmunoblastic-t-cell-lymphoma
#19
Dai Chihara, Michelle A Fanale, Roberto N Miranda, Mansoor Noorani, Jason R Westin, Loretta J Nastoupil, Fredrick B Hagemeister, Luis E Fayad, Jorge E Romaguera, Felipe Samaniego, Francesco Turturro, Hun J Lee, Sattva S Neelapu, M Alma Rodriguez, Michael Wang, Nathan H Fowler, Richard E Davis, L Jeffrey Medeiros, Chitra Hosing, Yago L Nieto, Yasuhiro Oki
Survival outcome of patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) who experience disease progression/relapse remains very poor. A total of 321 patients, newly diagnosed with PTCL-NOS (n = 180) or AITL (n = 141) between 1999 and 2015, were analysed. Failure-free survival (FFS) and overall survival (OS) were calculated from the time of first disease progression (FFS1, OS1), from second disease progression (FFS2, OS2) and from third progression (FFS3, OS3)...
March 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27982416/how-i-manage-peripheral-t-cell-lymphoma-not-otherwise-specified-and-angioimmunoblastic-t-cell-lymphoma-current-practice-and-a-glimpse-into-the-future
#20
REVIEW
Norbert Schmitz, Laurence de Leval
Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma (AITL) are the most frequent of more than 20 mature PTCL entities featuring a broad spectrum of morphological, immunophenotypic, molecular and clinical characteristics. Unfortunately, recent progress in understanding the (epi)genetic background of PTCL has not been met with similar advances in treatment. Thus, CHO(E)P [cyclophosphamide, doxorubicin, vincristine, and prednisone (plus etoposide)] remains standard first-line therapy...
March 2017: British Journal of Haematology
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