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https://www.readbyqxmd.com/read/28889481/a-review-of-the-biologic-and-clinical-significance-of-genetic-mutations-in-angioimmunoblastic-t-cell-lymphoma
#1
REVIEW
Kota Fukumoto, Tran B Nguyen, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients...
September 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28885361/angioimmunoblastic-t-cell-lymphoma-and-hypereosinophilic-syndrome-with-fip1l1-pdgfra-fusion-gene-effectively-treated-with-imatinib-a-case-report
#2
Masayo Yamamoto, Katsuya Ikuta, Yasumichi Toki, Mayumi Hatayama, Motohiro Shindo, Yoshihiro Torimoto, Toshikatsu Okumura
RATIONALE: Hypereosinophilic syndrome (HES) is a rare disorder characterized by hypereosinophilia and organ damage. Some cases of HES are caused by the FIP1L1/PDGFRA fusion gene and respond to imatinib. FIP1L1/PDGFRA-positive HES occasionally evolves into chronic eosinophilic leukemia or into another form of myeloproliferative neoplasm; however, the development of a malignant lymphoma is very rare. We present a rare case of angioimmunoblastic T-cell lymphoma (AITL) and HES with the FIP1L1/PDGFRA gene rearrangement...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28832024/activation-of-rhoa-vav1-signaling-in-angioimmunoblastic-t-cell-lymphoma
#3
M Fujisawa, M Sakata-Yanagimoto, S Nishizawa, D Komori, P Gershon, M Kiryu, S Tanzima, K Fukumoto, T Enami, M Muratani, K Yoshida, S Ogawa, K Matsue, N Nakamura, K Takeuchi, K Izutsu, K Fujimoto, T Teshima, H Miyoshi, P Gaulard, K Ohshima, S Chiba
Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA...
August 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28797780/clinical-practice-recommendations-on-indication-and-timing-of-hematopoietic-cell-transplantation-in-mature-t-cell-and-nk-t-cell-lymphomas-an-international-collaborative-effort-on-behalf-of-the-guidelines-committee-of-the-american-society-for-blood-and-marrow
#4
Mohamed A Kharfan-Dabaja, Ambuj Kumar, Ernesto Ayala, Mehdi Hamadani, Peter Reimer, Christian Gisselbrecht, Francesco d'Amore, Esa Jantunen, Takashi Ishida, Ali Bazarbachi, Francine Foss, Ranjana Advani, Timothy S Fenske, Hillard M Lazarus, Jonathan W Friedberg, Mahmoud Aljurf, Lubomir Sokol, Kensei Tobinai, Eric Tse, Linda J Burns, Julio C Chavez, Nishitha M Reddy, Ritsuro Suzuki, Sairah Ahmed, Auayporn Nademanee, Mohamad Mohty, Ajay K Gopal, Michelle A Fanale, Barbara Pro, Alison J Moskowitz, Anna Sureda, Miguel Angel Perales, Paul A Carpenter, Bipin N Savani
Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28753568/elevated-serum-interleukin-10-level-and-m2-macrophage-infiltration-are-associated-with-poor-survival-in-angioimmunoblastic-t-cell-lymphoma
#5
Jun Soo Ham, Ha Young Park, Kyung Ju Ryu, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Interleukin-10 (IL-10) induces an immunosuppressive microenvironment including M2 macrophages, inhibiting anti-tumor immunity. The aim of this study was to evaluate whether serum IL-10 level at diagnosis and tissue infiltration of M2 macrophages could predict survival outcome of patients with angioimmunoblastic T-cell lymphoma (AITL).We measured serum levels of IL-5, IL-10, IL-12, and interferon-gamma (IFN-γ) at diagnosis in AITL and other common subtypes of nodal T-cell lymphoma including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) or ALK-positive ALCL between September 2008 and December 2014...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28691928/mutations-in-5-methylcytosine-oxidase-tet2-and-rhoa-cooperatively-disrupt-t-cell-homeostasis
#6
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...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28634614/detection-of-the-circulating-tumor-dnas-in-angioimmunoblastic-t-cell-lymphoma
#7
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...
September 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28622960/treatment-of-peripheral-t-cell-lymphoma-in-community-settings
#8
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
#9
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 tumour cells, which have a T follicular helper (TFH) cell phenotype, and a surrounding and extensive tumour 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 haematopoietic progenitor cell. An article published recently in the Journal of Pathology describes the use of microdissection to isolate PD1(+) AITL tumour 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
April 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
#17
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
#18
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
#19
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
#20
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
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