High Expression of Intestinal Homing Receptor CD103 in Adult T-Cell Leukemia/Lymphoma, Similar to 2 Other CD8+ T-Cell Lymphomas

2016 ◽  
Vol 40 (4) ◽  
pp. 462-470 ◽  
Author(s):  
Hideki Ishibashi ◽  
Satoshi Nimura ◽  
Kenji Ishitsuka ◽  
Yasuhito Mihashi ◽  
Mikio Mizoguchi ◽  
...  
2019 ◽  
Vol 865 ◽  
pp. 172738 ◽  
Author(s):  
Tomohiro Kozako ◽  
Akiyoshi Aikawa ◽  
Takeo Ohsugi ◽  
Yu-ichiro Uchida ◽  
Naho Kato ◽  
...  

Blood ◽  
2010 ◽  
Vol 115 (5) ◽  
pp. 1026-1036 ◽  
Author(s):  
Javeed Iqbal ◽  
Dennis D. Weisenburger ◽  
Timothy C. Greiner ◽  
Julie M. Vose ◽  
Timothy McKeithan ◽  
...  

Abstract Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL–not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK+ ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1–induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5026-5026
Author(s):  
Neeraj Agnihotri ◽  
Yiwu Huang ◽  
Perry Gerard

Abstract Abstract 5026 Introduction Adult T cell leukemia/lymphoma(ATL) is a distinct peripheral T cell lymphocytic malignancy associated with a retrovirus Human T cell Lymphotropic Virus type I(HTLV I). Patients with aggressive ATL generally have a poor prognosis. Positron Emission Tomography (PET) scan is highly sensitive and specific in the imaging of B-cell lymphomas, however the use in T- cell lymphomas is less defined. PET scan images from the skull base to mid thigh only, are generally obtained for staging of these lymphomas. We demonstrate two cases in which inclusion of below the knee areas on the PET scan lead to detection of impending fractures and timely intervention preventing morbidity and delay in treatment. Case report Our first patient was a 45 year old African American female who presented to us with chief complaints of generalized lethargy and significant weight loss. Labs revealed hypercalcemia of 15 mg/dl which was treated emergently. CT scan of the chest abdomen and pelvis revealed lymphadenopathy in the subcarinal, bilateral hilar and posterior mediastinal areas and evidence of sclerotic foci in the pelvis and bilateral femoral heads. Bone marrow biopsy was done which showed peripheral T cell lymphoma with CD 3, CD 5 positive, CD 20 negative and CD 43 positive. In addition HTLV I antibody was positive by western blot analysis which confirmed the diagnosis of Adult T cell leukemia/lymphoma. Our second patient was a 32 year old Caribbean male who presented with diffuse cervical lymphadenopathy and weight loss over one month duration. Labs revealed hypercalcemia of 12.5 mg/dl, which was treated. Biopsy of the right cervical lymph node revealed a diagnosis of peripheral T cell lymphoma with CD 2, CD 3, CD 4 and CD 5 positive. HTLV I antibody was found positive confirming the diagnosis of Adult T cell leukemia/lymphoma. Bone marrow was also involved. In both of these patients, we obtained a whole body PET scan for staging with special instructions to obtain images from the skull to both feet, keeping in mind the presentation with hypercalcemia and the propensity of this particular malignancy to involve the bones. PET scan in the first patient revealed increased uptake in lymph node areas mentioned above. Interestingly, there were multiple foci of uptake in the lower extremities from pelvis to feet bilaterally with multiple lytic areas in cortical and medullary areas with an area of cortical disruption in right tibial area indicating an impending fracture. PET scan in the second patient revealed adenopathy in neck, chest, abdomen, osseous lesions in the sternum, vertebrae, several cortical lytic lesion in bilateral lower extremities and a lesion in right mid tibia extending into medullary space indicating an impending fracture. Based on PET scan results of below the knee impending fractures in both the patients, orthopedic evaluation was obtained prior to instituting chemotherapy. Patients were suggested to limit weight bearing on the affected side, thus preventing increased morbidity and delay in institution of chemotherapy from the possible fractures. Conclusions Limited data available on the use of PET in peripheral T cell lymphomas suggests that it is very sensitive and highly specific at diagnosing nodal and non cutaneous extra-nodal disease, but not very sensitive for cutaneous lesions. Skull base to proximal thigh imaging is generally recommended to survey the body in search for areas of abnormal tracer accumulation for most tumor types including lymphomas. In addition, asymptomatic patients are unlikely to have areas below mid thigh included in PET imaging. Our experience with using whole body PET imaging in these two cases of adult T cell leukemia/lymphoma demonstrates the increased diagnostic value of using whole body PET scan even in asymptomatic patients with this lymphoma. Both the patients had unstable bone lesions which would have been missed on a routine skull base to mid thigh PET scan with increased likelihood of a fracture. Therefore, skull base to feet whole body PET scan should be used for more accurate staging and assessment and to prevent increased morbidity and delay in treatment of these aggressive lymphomas. Disclosures No relevant conflicts of interest to declare.


Oncogene ◽  
2004 ◽  
Vol 24 (3) ◽  
pp. 419-430 ◽  
Author(s):  
Rihab Nasr ◽  
Marwan E El-Sabban ◽  
José-Antonio Karam ◽  
Ghassan Dbaibo ◽  
Youmna Kfoury ◽  
...  

2020 ◽  
Vol 4 (10) ◽  
pp. 2180-2191
Author(s):  
Masato Saito ◽  
Toshihiko Ishii ◽  
Itaru Urakawa ◽  
Asuka Matsumoto ◽  
Ayako Masaki ◽  
...  

Abstract Skin-related adverse events (AEs) occur frequently in adult T-cell leukemia-lymphoma (ATL) patients treated with mogamulizumab, a humanized anti-CCR4 monoclonal antibody. This study was undertaken to elucidate the mechanisms of mogamulizumab-induced skin-related AEs. We analyzed the T-cell receptor β chain repertoire in ATL patients’ peripheral blood mononuclear cells (PBMCs) before and after mogamulizumab. Skin-related AEs were present in 16 patients and were absent in 8 patients. Additionally, we included 11 patients before and after chemotherapy without mogamulizumab. Immune-related gene expression in PBMCs before and after mogamulizumab was also assessed (n = 24). Mogamulizumab treatment resulted in CCR4+ T-cell depletion, and the consequent lymphopenia provoked homeostatic CD8+ T-cell proliferation, as evidenced by increased expressions of CD8B and CD8A, which were significantly greater in patients with skin-related AEs than in those without them. We hypothesize that proliferation is driven by the engagement of self-antigens, including skin-related antigens, in the face of regulatory T-cell depletion. Together with the observed activated antigen presentation function, this resulted in T-cell diversification that was significantly greater in patients with skin-related AEs than in those without. We found that the CD8+ T cells that proliferated and diversified after mogamulizumab treatment were almost entirely newly emerged clones. There was an inverse relationship between the degree of CCR4+ T-cell depletion and increased CD8+ T-cell proliferation and diversification. Thus, lymphocyte-depleting mogamulizumab treatment provokes homeostatic CD8+ T-cell proliferation predominantly of newly emerging clones, some of which could have important roles in the pathogenesis of mogamulizumab-induced skin-related AEs.


Blood ◽  
2016 ◽  
Vol 127 (5) ◽  
pp. 596-604 ◽  
Author(s):  
Yasunobu Nagata ◽  
Kenji Kontani ◽  
Terukazu Enami ◽  
Keisuke Kataoka ◽  
Ryohei Ishii ◽  
...  

Key Points RHOA mutations are common in ATLL and show a unique distribution compared with other T-cell lymphomas. Depending on patients, functionally distinct RHOA mutations are clonally selected and involved in the pathogenesis of ATLL.


2012 ◽  
Vol 131 (9) ◽  
pp. 2044-2055 ◽  
Author(s):  
Tomohiro Kozako ◽  
Akiyoshi Aikawa ◽  
Teruhisa Shoji ◽  
Takahiro Fujimoto ◽  
Makoto Yoshimitsu ◽  
...  

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