Flow Cytometric Immunophenotyping of Adult T-Cell Leukemia/Lymphoma Using CD3 Gating

Yokote, Taiji; Akioka, Toshikazu; Oka, Shiro; Hara, Satoshi; Kobayashi, Kichinosuke; Nakajima, Hideto; Yamano, Takeshi; Ikemoto, Toshiyuki; Shimizu, Akira; Tsuji, Motomu; Hanafusa, Toshiaki

doi:10.1309/ken4mxm5y9a1gemp

Cited by 37 publications

(11 citation statements)

References 14 publications

(21 reference statements)

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“…[14][15][16][17][18] PTCLs have also been reported during CD3-CD4 + L-HES course. 6,9,[19][20][21][22][23][24] Two of 23 patients currently followed in the French Eosinophil Network, and one more patient recently reported by others, 25 developed well-defined AITL several years after L-HES diagnosis, which thus raised the problem of the diagnosis of well-defined T-cell lymphoma in patients who have clonal circulating T cells.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 96%

CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o neral T-cell lymphomas (PTCL) but mainly in angioimmunoblastic T-cell lymphoma (AITL). [14][15][16][17][18] PTCLs have also been reported during CD3-CD4 + L-HES course. 6,9,[19][20][21][22][23][24] Two of 23 patients currently followed in the French Eosinophil Network, and one more patient recently reported by others, 25 developed well-defined AITL several years after L-HES diagnosis, which thus raised the problem of the diagnosis of well-defined T-cell lymphoma in patients who have clonal circulating T cells.In this study, we focused on the lymphoid infiltrates in lymph nodes, skin and other available biopsies of tissue involved in L-HES, to assess the presence of clonal T cells at diagnosis and during CD3 - CD4+ L-HES course. We secondly aimed to distinguish L-HES from AITL by comparing histopathological and immunophenotypic characteristics between both entities Methods PatientsTwenty-three hypereosinophilic syndrome (HES) patients with a documented presence of CD3 - CD4+ aberrant subset and a negative FIP1L1-PDGFRA fusion gene research are currently followed The clonal T-cell disease in CD3 -CD4 + L-HES haematologica | 2015; 100(8) 1087 © F e r r a t a S t o r t i F o u n d a t i o nSkin lesions in L-HES patients were pruritic papulo-nodular inpatients P1 and P2, pruritic papular lesions in patient P3, P5, P8, isolated pruritus in patients P7 and P9. Numbers in in the French Eosinophil Network. For the present study, 16 patients (P1-P16) were included, 12 of them had available tissue biopsies during L-HES course. All satisfied criteria for HES (n=15) or hypereosinophilia (HE) (n=1, P13, no organ damage or clinical manifestation) criteria in accordance with the latest up-dated consensus definitions.1 Main clinical characteristics are summarized in Table 1. For the 7 remaining patients, no complementary lymphocyte immunophenotyping was performed, no biopsy was performed (n=5) or biopsies were not available for analysis (n=2). The study was approved by the Lille Hospital Ethical Committee and carried out in accordance with the Declaration of Helsinki.Ten of these patients had bone marrow biopsies at CD3 -CD4 + L-HES diagnosis in order to exclude a T-cell lymphoma (Patients P2-4, P8, P9, P11, P12, P14-16) (data not shown). Four patients had lymph nodes biopsies for a suspicion of T-cell lymphoma during follow up (Patients P1, P3, P4 and P10). For this work, all their biopsies were retrieved for further investigation and for a centralized compared analysis to be made.Finally, Patients P4 and P16 developed a well-defined AITL during L-HES course (AITL/L-HES patients).Patient P4. Patient P4 was 18-years old when a CD3 -CD4 + L-HES diagnosis was made in 1999 and was previously reported by us. 26He presented with eczema-like lesions, rare episodes of angioedema and multiple adenopathy. Despite high circulating CD3 -CD4 + T-cell count (28 G/L), lymph node histological examination confirmed lymphoid reactive hyperplasia. As he was in really good G. Lefèvre ...

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 96%

CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

et al. 2015

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“…This is similar to the T-cell marker phenotype commonly observed for ATL cells in humans with the disease. 22 HTLV-1 transformation of human T cells has been associated with production of multiple cytokines that likely play important roles in pathogenesis. 23 We therefore examined the kinetics of cytokine production in the LTR-Tax CD4 ϩ T-cell cultures.…”

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confidence: 99%

Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells

Swaims¹,

Khani

Zhang³

et al. 2010

Blood

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Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/ lymphoma (ATL). IntroductionHuman T-cell Leukemia Virus-1 (HTLV-1) is a CD4 ϩ T cell-tropic human deltaretrovirus infecting 10-20 million people worldwide. 1,2 HTLV-1 was the first human retrovirus isolated and is the causative agent of diverse diseases such as Adult T-cell Leukemia/ Lymphoma (ATL), a fatal CD4 ϩ T-cell Leukemia/Lymphoma and HTLV-1 Acquired Myelopathy/Tropical Spastic Paraparesis (HAM-TSP), a demyelinating disease of the spinal cord. Approximately 3%-5% of those infected with HTLV-1 will develop disease, while the majority of carriers remain asymptomatic. Development of HAM/TSP or ATL occurs after long clinically latent periods and specific disease phenotypes tend to be associated with particular routes and timing of infection. 3 The mechanisms responsible for HTLV-1 pathogenesis remain poorly understood.Development of HTLV-1-associated diseases is dependent upon expression of HTLV-1 gene products, most notably the HTLV-1 viral transcriptional transactivator, Tax 4 and other regulatory proteins including the HBZ protein. 5,6 Tax expression is required for viral replication, and can induce CD4 ϩ T-cell immortalization. Tax enhances viral gene expression through interactions with cellular transcription factors at the HTLV-1 Long Terminal Repeat (LTR) promoter. Tax also interacts with many host proteins involved in cell survival, proliferation, genomic stability, and cell cycle regulation to promote altered cellular gene expression. 4 Thus, Tax plays a critical role in regulating viral gene expression, as well as the host cellular response to infection. Recently, HBZ has also been shown to play an important role in HTLV-1 pathogenesis both through increased viral load, and enhancing T-cell proliferation in culture and transgenic mice. 7,8 p12 I , an activator of STAT5 antiapoptotic signaling is also likely to play a role in HTLV-1 transformation. 9 Determining the cellular and viral events that regulate HTLV-1 gene expression is central to understanding pathogenesis of HTLV-1 infection. Our laboratory has previously shown that Tax expression in chronically infected human CD4 ϩ T cells can be markedly enhanced by immune activation stimuli, such as PMA, PHA, or anti-CD3 antibody. 10,11 These data suggest that immune stimulation of infected cells, through T-cell antigen receptor signaling, could regulate a balance of virus-host interactions leading to increased viral gene expression.To elucidate whether immune activation events contribute to HTLV-1-associated-diseases, study of animal models of pathogenesis will be valuable. Although mouse models of Tax-associated oncogenesis have been described, 12-14 a transgenic model of Tax-derived CD4 ϩ T-cell oncogenesis, reflecting regulation of Tax by the authentic HTLV-1 LTR has yet to be established. Transgenic mice expressing Tax under the control of the LTR, are phenotypically normal until approximately 3 months of age, when they deve...

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“…For a number of cases with a limited number of lymphoma cells involving bone marrow, FCM may assist with diagnosis (18,19). However, there may be different results between BMA/BMB and FCM (20,21).…”

Section: Discussionmentioning

confidence: 95%

A unique bone marrow lymphoma patient presenting with an isolated mass: A case report

Duan

2017

Oncol Lett

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Abstract. Bone marrow lymphoma with the onset of an isolated mass in the bone marrow is extremely rare. The present case report described a unique case of B cell lymphoblastic lymphoma (LBL) presenting with an isolated mass in the bone marrow cavity, without any organopathy or lymphadenopathy. An isolated mass in bone marrow is a rare primary manifestation of LBL. The patient in the present case report presented with pain in the right elbow, a fever, pancytopenia and splenomegaly. Additionally, no abnormality was determined in the lymph nodes, the bone marrow karyotype or a computed tomography scan of the humerus. Positron emission tomography (PET) examination revealed an increased uptake of 18 F-fluorodeoxyglucose in right distal humerus. An isolated mass in the bone marrow cavity was removed by surgery. Pathological findings revealed B cell LBL. The patient received an acute lymphocytic leukemia chemotherapy regimen and achieved complete remission. However, 4 months following the initial diagnosis, the patient succumbed due to a relapse. The present case highlighted the importance of PET examination and biopsy, and the requirement to identify appropriate treatments for LBL. Additionally, it is important to broaden the differential diagnosis when an isolated mass is identified in the bone marrow cavity.

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Flow Cytometric Immunophenotyping of Adult T-Cell Leukemia/Lymphoma Using CD3 Gating

Cited by 37 publications

References 14 publications

CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells

A unique bone marrow lymphoma patient presenting with an isolated mass: A case report

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