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Ambroise Marçais, Laetitia Waast, Julie Bruneau, Katia Hanssens, Vahid Asnafi, Philippe Gaulard, Felipe Suarez, Patrice Dubreuil, Antoine Gessain, Olivier Hermine, Claudine Pique
Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells...
November 26, 2016: Oncotarget
Shigeo Fuji, Takero Shindo
Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory...
2016: Stem Cell Investigation
R Moles, X T Bai, H Chaib-Mezrag, C Nicot
BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATLL), a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the "Werner syndrome ATP-dependent helicase" encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells...
November 9, 2016: Journal of Hematology & Oncology
Bailong Liu, Bin Liu, Xu Wang, Liang Guo, Xiaoliang Liu, Wei Han, Lihua Dong, Min Liu
BACKGROUND: Relapse of acute lymphoblastic leukemia (ALL) occurring in the breast after allografting is extremely rare, with only 22 reported cases in the literature thus far. Further, the lack of a systemic analysis provides little information about this entity. We present a case of isolated extramedullary relapse from acute T lymphoblastic leukemia (ATLL) after allogeneic hematopoietic stem cell transplantation (HSCT). CASE PRESENTATION: A 32-year-old Chinese woman diagnosed with ATLL with myeloid antigen expression received HSCT from her human leukocyte antigen (HLA)-matched sister and presented with two lesions in her right breast 6 months later...
November 9, 2016: BMC Cancer
Achiléa L Bittencourt, Agnes Carvalho Andrade, Cristiane Requião, Maria da Gloria Bomfim Arruda, Iguaracyra Araújo
Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+...
October 24, 2016: Brazilian Journal of Infectious Diseases
Sayed Hamid Reza Mozhgani, Najmeh Jaberi, Seyyed Abdolrahim Rezaee, Reza Bustani, Seyyed Mohammad Jazayeri, Mohammad Mahdi Akbarian, Saeideh Milani, Hanieh Tarokhian, Mehdi Norouzi
Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although HTLV-1 proviral load (PVL) has been introduced as a risk factor for these diseases' progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN λ3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs)...
October 27, 2016: Journal of Medical Virology
Kaname Miyashita, Kei Fujii, Kenichi Taguchi, Mototsugu Shimokawa, Mitsuaki A Yoshida, Yasunobu Abe, Jun Okamura, Shinya Oda, Naokuni Uike
PURPOSE: Microsatellite instability (MSI) has been a long-standing biomarker candidate for drug resistance in tumour cells. Despite numerous clinical studies, the data in the literature are not conclusive. The complexity of the MSI phenomenon in some malignancies may, at least partly, account for the discrepancy. In addition, methodological problems are also pointed out in the assay techniques. We previously established a unique fluorescent technique in which the major methodological problems in conventional assays are overcome...
October 25, 2016: Journal of Cancer Research and Clinical Oncology
Giang Huong Nguyen, James Y Wang, Kenneth B Hymes, Cynthia M Magro
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities...
October 12, 2016: American Journal of Dermatopathology
Junki Kato, Ayako Masaki, Keiichiro Fujii, Hisashi Takino, Takayuki Murase, Kentaro Yonekura, Atae Utsunomiya, Takashi Ishida, Shinsuke Iida, Hiroshi Inagaki
Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non-quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T-cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers...
September 27, 2016: Pathology International
Takashi Ishida, Hiroshi Fujiwara, Kisato Nosaka, Naoya Taira, Yasunobu Abe, Yoshitaka Imaizumi, Yukiyoshi Moriuchi, Tatsuro Jo, Kenichi Ishizawa, Kensei Tobinai, Kunihiro Tsukasaki, Shigeki Ito, Makoto Yoshimitsu, Maki Otsuka, Michinori Ogura, Shuichi Midorikawa, Wanda Ruiz, Tomoko Ohtsu
Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yukie Tsubokura, Atsushi Satake, Masaaki Hotta, Hideaki Yoshimura, Shinya Fujita, Yoshiko Azuma, Takahisa Nakanishi, Aya Nakaya, Tomoki Ito, Kazuyoshi Ishii, Shosaku Nomura
A humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab (MOG), has been shown to be safe and effective in the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL). MOG depletes ATLL cells as well as regulatory T cells (Tregs), as CCR4 is expressed on these cells as well. In this context, pretransplant treatment with MOG may induce severe graft-versus-host disease (GVHD) in allogeneic hematopoietic stem-cell transplantation (HSCT). However, the influence of MOG on allogeneic HSCT, including its induction of GVHD, is unclear...
August 29, 2016: International Journal of Hematology
Horlad Hasita, Chaoya Ma, Hiromu Yano, Cheng Pan, Koji Ohnishi, Yukio Fujiwara, Shinya Endo, Yoshitaka Kikukawa, Yutaka Okuno, Masao Matsuoka, Motohiro Takeya, Yoshihiro Komohara
Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domain-containing molecule-3. In the present study, we investigated expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin embedded tissue samples, and subsequently studied the detailed mechanism of up-regulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines...
August 26, 2016: Cancer Science
Hiromi Nagano, Yuichi Kurono, Kakushi Matushita
OBJECTIVE: One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV-1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients. METHODS: The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013...
August 20, 2016: Auris, Nasus, Larynx
Christa Roe, Rami Komrokji, Ling Zhang, Samantha Price, Lubomir Sokol
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is aggressive mature T-cell lymphoproliferative disorder with a poor outcome. METHODS: We present 10 patients with acute and lymphomatous subtypes of ATLL treated with distinct induction regimens, including CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], prednisone or prednisolone), interferon/zidovudine, and VCAP-AMP-VECP (vincristine, cyclophosphamide, doxorubicin, prednisone; doxorubicin, ranimustine, prednisone; vindesine, etoposide, carboplatin, prednisone)...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken-Ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Hasita Horlad, Koji Ohnishi, Chaoya Ma, Yukio Fujiwara, Daisuke Niino, Koichi Ohshima, Masahisa Jinushi, Masao Matsuoka, Motohiro Takeya, Yoshihiro Komohara
Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples...
August 2016: Oncology Letters
Hiroaki Miyoshi, Junichi Kiyasu, Takeharu Kato, Noriaki Yoshida, Joji Shimono, Shintaro Yokoyama, Hiroaki Taniguchi, Yuya Sasaki, Daisuke Kurita, Keisuke Kawamoto, Koji Kato, Yoshitaka Imaizumi, Masao Seto, Koichi Ohshima
Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7...
September 8, 2016: Blood
Hisayoshi Kondo, Midori Soda, Norie Sawada, Manami Inoue, Yoshitaka Imaizumi, Yasushi Miyazaki, Masako Iwanaga, Yasuhito Tanaka, Masashi Mizokami, Shoichiro Tsugane
BACKGROUND AND PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1); no effective methods have yet been identified to prevent development of ATLL in carriers of HTLV-1. This study investigated the association between cigarette smoking and the risk of ATLL development among Japanese carriers of HTLV-1. METHODS: This study examined the association between smoking and development of ATLL in a cohort of 1,332 Japanese HTLV-1 carriers aged 40-69 years free of ATLL at baseline from two different HTLV-1-endemic areas of Japan...
September 2016: Cancer Causes & Control: CCC
Sakura Aoki, Sanaz Firouzi, Yosvany López, Tadanori Yamochi, Kazumi Nakano, Kaoru Uchimaru, Atae Utusnomiya, Masako Iwanaga, Toshiki Watanabe
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the transformation of HTLV-1-infected T cells. ATLL, especially its aggressive form, is known for its poor prognosis, even with intensive chemotherapy. ATLL cells are considered to be monoclonal; however, multiclonal proliferation or emergence of a new clone over time has been reported based on Southern blot analysis, although direct molecular evidence remains elusive. Furthermore, it is thought that clonal change may be a cause of early drug resistance in ATLL...
September 2016: International Journal of Hematology
Takahiro Shima, Kenjiro Kamezaki, Kazuhiko Higashioka, Shuichiro Takashima, Goichi Yoshimoto, Koji Kato, Tsuyoshi Muta, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Koichi Akashi
A 74-year-old woman with refractory adult T-cell leukemia/lymphoma (ATLL) received three courses of mogamulizumab. Despite obtaining complete remission, she thereafter presented with progressive ascites. An analysis of the ascites and laboratory tests revealed no evidence of ATLL invasion, infectious disease, or liver cirrhosis. The mogamulizumab concentrations were maintained in the ascites at approximately 10-15% of that in the plasma. Mogamulizumab was considered to be a plausible pathogenesis of her ascites...
2016: Internal Medicine
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