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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, Yasuhiro Oki
We performed a retrospective analysis to identify risk factors and survival outcome for central nervous system (CNS) relapse of peripheral T-cell lymphoma (PTCL) by histologic type. Records of 600 PTCL patients diagnosed between 1999 and 2014 were analyzed including PTCL not otherwise specified (PTCL-NOS, 174 patients), angoimmunoblastic T-cell lymphoma (AITL, 144), ALK+anaplastic large cell lymphoma (ALCL, 74), ALK-ALCL (103), extranodal NK-cell lymphoma (ENKL, 54), or others (51). With a median follow up of 57 months, 13 patients (4 PTCL-NOS, 1 AITL, 4 ALK+ALCL, 2 ALK-ALCL, 2 ENKL) experienced CNS relapse...
2018: PloS One
Sharna Tanzima Nuhat, Mamiko Sakata-Yanagimoto, Daisuke Komori, Keiichiro Hattori, Yasuhito Suehara, Kota Fukumoto, Manabu Fujisawa, Manabu Kusakabe, Kosei Matsue, Hirotake Wakamatsu, Mitsunobu Shimadzu, Shigeru Chiba
Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of nodal peripheral T-cell lymphomas. Somatic RHOA mutations, most frequently found at the hotspot site c.50G>T, p. Gly17Val (G17V RHOA mutation) are a genetic hallmark of AITL. Detection of the G17V RHOA mutations assists prompt and appropriate diagnosis of AITL. However, an optimal detection method for the G17V RHOA mutation remains to be elucidated. We compared the sensitivity and concordance of next generation sequencing (NGS), droplet digital PCR (ddPCR) and PNA-LNA clamp method for detecting the G17V RHOA mutations...
March 1, 2018: Cancer Science
Jingxia Jin, Cuiping Zheng, Shenghao Wu
INTRODUCTION: Angioimmunoblastic T-cell lymphoma (AITL) is a kind of rare peripheral T cell lymphoma, which usually has acute onset at old age. MATERIALS AND METHODS: Here we report a case of relapsed refractory AITL, which has achieved obvious curative effect after treatment with chidamide. RESULTS: Initially, the patient received 7 courses of treatment with recombinant human endostatin (endostar)+CHOP. The patient achieved complete remission, but suffered from recurrence later...
January 2018: Medicine (Baltimore)
Ya-Ting Hsu, Hui-Jen Tsai, Jeffrey S Chang, Sin-Syue Li, Jih-Luh Tang, Su-Peng Yeh, Wen-Li Hwang, Jin-Hwang Liu, Tran-Der Tan, Po-Nan Wang, Hui-Hua Hsiao, Tsai-Yun Chen
T-cell lymphomas are generally aggressive malignancies with poor prognosis. There are no standard treatment guidelines for T-cell lymphomas, and the timing of stem cell transplantation (SCT) is not well known. In this study, we investigated the outcomes of Taiwanese patients with T-cell lymphomas after SCT. We retrospectively analyzed 131 patients with T-cell lymphomas receiving SCT (autologous: 90, allogeneic: 41) from 2009 to 2014. More autologous SCT recipients were ALCL or in complete remission, and more allogeneic recipients had advanced disease...
February 12, 2018: Bone Marrow Transplantation
Shun-Ichi Wakabayashi, Takefumi Kimura, Naoki Tanaka, Satoru Joshita, Kazuhito Kawata, Takeji Umemura, Yuki Hiroshima, Hiromitsu Mori, Hikaru Kobayashi, Shuichi Wada, Eiji Tanaka
A 68-year-old woman was referred to our hospital due to fever and rash on the neck and extremities. Laboratory findings revealed hepatic dysfunction and positivity for anti-mitochondrial M2 antibody (AMA-M2). Hepatosplenomegaly and systemic lymphadenopathy were detected by enhanced computed tomography. One week after her first visit, hypoxemia, ascites, and Coomb test-positive autoimmune hemolytic anemia had newly appeared in addition to worsened fever, hepatosplenomegaly, and lymphadenopathy. Results of axillary lymph node, skin, and bone-marrow biopsies led to the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), for which CEPP therapy (cyclophosphamide, etoposide, procarbazine, and prednisolone) was initiated...
February 10, 2018: Clinical Journal of Gastroenterology
Jose R Cortes, Alberto Ambesi-Impiombato, Lucile Couronné, S Aidan Quinn, Christine S Kim, Ana C da Silva Almeida, Zachary West, Laura Belver, Marta Sanchez Martin, Laurianne Scourzic, Govind Bhagat, Olivier A Bernard, Adolfo A Ferrando, Teresa Palomero
Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4+ T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling...
February 1, 2018: Cancer Cell
Manabu Fujisawa, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) has been classified as a subtype of mature T-cell neoplasms. The recent revision of the WHO classification proposed a new category of nodal T-cell lymphoma with follicular helper T (TFH)-cell phenotype, which was classified into three diseases: AITL, follicular T-cell lymphoma, and nodal peripheral T-cell lymphoma with TFH phenotype. These lymphomas are defined by the expression of TFH-related antigens, CD279/PD-1, CD10, BCL6, CXCL13, ICOS, SAP, and CXCR5. Although recurrent mutations in TET2, IDH2, DNMT3A, RHOA, and CD28, as well as gene fusions, such as ITK-SYK and CTLA4-CD28, were not diagnostic criteria, they may be considered as novel criteria in the near future...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
Siok-Bian Ng, Shuangyi Fan, Shoa-Nian Choo, Michal Hoppe, Hoang Mai Phuong, Sanjay De Mel, Anand D Jeyasekharan
Immunohistochemistry (IHC) provides clinically useful information on protein expression in cancer cells. However, quantification of colocalizing signals using conventional IHC and visual scores is challenging. Here we describe the application of quantitative immunofluorescence in angioimmunoblastic T-cell lymphoma (AITL), a peripheral T-cell lymphoma characterized by cellular heterogeneity that impedes IHC interpretation and quantification. A multiplexed immunofluorescence (IF) panel comprising T- and B-lymphocyte markers along with T-follicular helper (TFH) markers was validated for appropriate cellular localization in sections of benign tonsillar tissue and tested in two samples of AITL, using a Vectra microscope for spectral imaging and InForm software for analysis...
December 1, 2017: SLAS Technology
Igor Buchwalow, Dmitri Atiakshin, Vera Samoilova, Werner Boecker, Markus Tiemann
Endogenous cell autofluorescence is a common nuisance that complicates the use of fluorescence microscopy. When using fluorescence-labeled antibodies for specific cell labeling in tissue sections of human angioimmunoblastic T-cell lymphoma (AITL), we encountered with a problematic autofluorescence of multiple cells. These cells emitted fluorescence signals in the green, red and deep-red spectral range. Characterization of these autofluorescent cells solely on the basis of their autofluorescence failed. To identify these enigmatic cells residing the lymphoma tissue, we combined two imaging techniques-fluorescence and brightfield microscopy...
February 2018: Histochemistry and Cell Biology
Mary Gleeson, Clare Peckitt, David Cunningham, Adam Gibb, Eliza A Hawkes, Morgan Back, Binnaz Yasar, Kate Foley, Rebecca Lee, Joanna Dash, Hannah Johnson, Catherine O'Hara, Andrew Wotherspoon, Ayoma Attygalle, Lia Menasce, Patrick Shenjere, Mike Potter, Mark E Ethell, Claire Dearden, John Radford, Ian Chau, Kim Linton
We evaluated the outcomes for patients with peripheral T-cell lymphoma (PTCL) undergoing front-line chemotherapy at our institutions between 2002 and 2012. One hundred and fifty-six patients were eligible, comprising PTCL not otherwise specified (NOS) (n = 50, 32.0%), angioimmunoblastic T-cell lymphoma (AITL) (n = 44, 28.2%), anaplastic large-cell lymphoma (ALCL) ALK negative (n = 23, 14.7%), ALCL ALK positive (n = 16, 10.3%), and other (n = 23, 14.7%). Most patients received CHOP (66.0%) and 13...
November 9, 2017: Leukemia & Lymphoma
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...
September 29, 2017: Oncotarget
Ying Li, Chunmei Yang, Liping Mao, Jinghan Wang, Chenying Li, Wenbin Qian
Angioimmunoblastic T-cell lymphoma (AITL) is a major subtype of peripheral T-cell lymphoma (PTCL). Due to its low incidence, the characteristics of AITL are still not well understood. The prognostic evaluation of this disease has not been established.We retrospectively analyzed 52 patients with newly diagnosed AITL in China between January 2008 and September 2016.Among these patients, the median age at diagnosis was 62 (40-83) and 58% (30/52) of the patients were older than 60 years. Thirty-five patients were male, accounting for 67...
September 2017: Medicine (Baltimore)
Yosuke Matsumoto, Hisao Nagoshi, Mihoko Yoshida, Seiichi Kato, Junya Kuroda, Kazuho Shimura, Hiroto Kaneko, Shigeo Horiike, Shigeo Nakamura, Masafumi Taniwaki
Objective It has been postulated that the normal counterpart of angioimmunoblastic T-cell lymphoma (AITL) is the follicular helper T-cell (TFH). Recent immunological studies have identified several transcription factors responsible for T-cell differentiation. The master regulators associated with T-cell, helper T-cell (Th), and TFH differentiation are reportedly BCL11B, Th-POK, and BCL6, respectively. We explored the postulated normal counterpart of AITL with respect to the expression of the master regulators of T-cell differentiation...
November 1, 2017: Internal Medicine
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 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...
March 2018: Cancer Science
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)
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
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...
November 2017: Biology of Blood and Marrow Transplantation
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
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
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
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