Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
Biomark Med ; 14(18): 1703-1715, 2020 12.
Article in English | MEDLINE | ID: mdl-33140976

ABSTRACT

Background: Massive monoclonal or oligoclonal expansion of CD8+ T cells is a notable feature of primary infections of the Epstein-Barr virus (EBV). However, the clinical significance of this expansion is not clear. Results: An increase in the CD8dimCD3+ lymphocyte subset in patients with active EBV infection was due to caspase-8-dependent apoptosis was found using flow cytometry in this study. The number of these cells was associated with the illness severity. Pan-T-cell antigen and receptor analyses were also compared in patients with active EBV infections and T-cell large granular lymphocytic leukemia to provide additional diagnostic information. Conclusion: The increase in CD8dimCD3+ cells could be a biomarker of active EBV infection and an exclusion indicator of T-cell large granular lymphocytic leukemia with flow cytometric analysis.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/immunology , Fever/immunology , Leukemia, Large Granular Lymphocytic/diagnosis , Adult , Apoptosis/immunology , Biomarkers/blood , CD3 Complex/immunology , Caspase 8/immunology , Caspase 8/metabolism , Epstein-Barr Virus Infections/virology , Female , Fever/virology , Flow Cytometry/methods , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/isolation & purification , Humans , Leukemia, Large Granular Lymphocytic/immunology , Leukemia, Large Granular Lymphocytic/virology , Lymphocyte Subsets/immunology , Lymphocytes/immunology , Male , Middle Aged , Severity of Illness Index
3.
Pathology ; 52(1): 111-127, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31767131

ABSTRACT

Epstein-Barr virus (EBV)-positive T-cell and natural killer (NK)-cell lymphoproliferative diseases (EBV-TNKLPD) are a group of uncommon disorders characterised by EBV infection of T- and NK-cells. As a group, EBV-TNKLPD are more commonly encountered in Asians and Native Americans from Central and South America compared to Western populations. They encompass a spectrum of entities that range from non-neoplastic lesions such as EBV-associated haemophagocytic lymphohistiocytosis (EBV-HLH) to more chronic conditions with variable outcomes such as chronic active EBV infections (CAEBV) of T- and NK-cell type (cutaneous and systemic forms) and malignant diseases such as systemic EBV-positive T-cell lymphoma of childhood, aggressive NK-cell leukaemia, extranodal NK/T-cell lymphoma, nasal-type, and primary EBV-positive nodal T/NK-cell lymphoma. Due to their rarity, broad clinicopathological spectrum and significant morphological and immunophenotypic overlap, the diagnosis and precise classification of EBV-TNKLPD often pose a challenge to clinicians and pathologists. Correct classification of this group of rare diseases relies heavily on the age of onset, disease presentation, duration of symptoms and cell of origin (T- vs NK-cell lineage). In this review, we provide an update on the clinicopathological and molecular features of the various EBV-TNKLPD entities occurring in non-immunocompromised patients and present a practical algorithmic approach for the general pathologist who is confronted with these disorders in routine clinical practice.


Subject(s)
Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/pathogenicity , Killer Cells, Natural/pathology , Lymphoma, T-Cell/pathology , Lymphoproliferative Disorders/pathology , Epstein-Barr Virus Infections/diagnosis , Humans , Killer Cells, Natural/virology , Leukemia, Large Granular Lymphocytic/diagnosis , Leukemia, Large Granular Lymphocytic/pathology , Leukemia, Large Granular Lymphocytic/virology , Lymphoma, T-Cell/virology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/virology
4.
BMC Med Genomics ; 12(1): 88, 2019 06 17.
Article in English | MEDLINE | ID: mdl-31208405

ABSTRACT

BACKGROUND: Large granular lymphocyte (LGL) leukemia is an uncommon cancer characterized by sustained clonal proliferation of LGL cells. Antibodies reactive to retroviruses have been documented in the serum of patients with LGL leukemia. Culture or molecular approaches have to date not been successful in identifying a retrovirus. METHODS: Because a retrovirus must integrate into the genome of an infected cell, we focused our efforts on detecting a novel retrovirus integration site in the clonally expanded LGL cells. We present a new computational tool that uses long-insert mate pair sequence data to search the genome of LGL leukemia cells for retrovirus integration sites. We also utilize recently published methods to interrogate the status of polymorphic human endogenous retrovirus type K (HERV-K) provirus in patient genomes. RESULTS: Our data show that there are no new retrovirus insertions in LGL genomes of LGL leukemia patients. However, our insertion call tool did detect four HERV-K provirus integration sites that are polymorphic in the human population but absent from the human reference genome, hg19. To determine if the prevalence of these or other polymorphic proviral HERV-Ks differed between LGL leukemia patients and the general population, we used a recently developed tool that reports sites in the human genome occupied by a known proviral HERV-K. We report that there are significant differences in the number of polymorphic HERV-Ks in the genomes of LGL leukemia patients of European origin compared to individuals with European ancestry in the 1000 genomes (KGP) data. CONCLUSIONS: Our study confirms that the clonal expansion of LGL cells in LGL leukemia is not driven by the integration of a new infectious or endogenous retrovirus, although we do not rule out that these cells are responding to retroviral antigens produced in other cell types. However, our computational analyses revealed that the genomes of LGL leukemia patients carry a higher burden of polymorphic HERV-K proviruses compare to individuals from KGP of European ancestry. Our research emphasizes the merits of comprehensive genomic assessment of HERV-K in cancer samples and suggests that further analyses to determine contributions of HERV-K to LGL leukemia are warranted.


Subject(s)
Genome, Human/genetics , Leukemia, Large Granular Lymphocytic/genetics , Leukemia, Large Granular Lymphocytic/virology , Proviruses/physiology , Retroviridae/physiology , Virus Integration/genetics , Humans
5.
J Pediatr Hematol Oncol ; 41(5): e336-e337, 2019 07.
Article in English | MEDLINE | ID: mdl-29889803

ABSTRACT

Epstein-Barr virus (EBV)-positive aggressive natural killer-cell leukemia (ANKL) is a rare malignancy of mature natural killer cells, with a very poor survival rate. Patients have a rapidly declining clinical course and a poor prognosis, with a median survival of only a few months. Herein, we describe a 16-year-old boy who was diagnosed with EBV-positive ANKL and successfully treated using combination chemotherapy and a subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT). The patient is disease free 4 years and 9 months after alloHSCT. Thus, combination chemotherapy followed by alloHSCT seems to be a promising therapeutic option for EBV-positive ANKL.


Subject(s)
Combined Modality Therapy/methods , Herpesvirus 4, Human , Leukemia, Large Granular Lymphocytic/therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia, Large Granular Lymphocytic/virology , Male , Transplantation, Homologous/methods
6.
Int J Hematol ; 105(4): 540-544, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27830541

ABSTRACT

Aggressive NK-cell leukemia (ANKL) is characterized by systemic infiltration of Epstein-Barr virus (EBV)-associated natural killer cells and poor prognosis. We report a case of ANKL in which EBV-specific cytotoxic T lymphocytes (CTLs) were induced. A 41-year-old male suffered from fever, pancytopenia, and hepatosplenomegaly. The number of abnormal large granular lymphocytes in the bone marrow was increased and the cells were positive for CD56 and EBV-encoded small nuclear RNAs. The patient was diagnosed with ANKL and achieved a complete response following intensive chemotherapy. He then underwent allogeneic peripheral blood stem cell transplantation from his sister. Conditioning therapy consisted of total body irradiation and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of cyclosporine and methotrexate. On day 31, complete donor chimerism was achieved and no acute graft-versus-host disease developed. The ANKL relapsed on day 80, and cyclosporine was rapidly tapered and chemotherapy was started. During hematopoietic recovery, the number of atypical lymphocytes increased, but they were donor-derived EBV-specific CTLs. The patient achieved a partial response and EBV viral load decreased to normal range. Unfortunately, ANKL worsen again when the CTLs disappeared from his blood. This is the first case report of ANKL in which induced EBV-specific CTLs may have contributed to disease control.


Subject(s)
Herpesvirus 4, Human , Leukemia, Large Granular Lymphocytic/therapy , Peripheral Blood Stem Cell Transplantation/adverse effects , T-Lymphocytes, Cytotoxic/virology , Adult , Disease Management , Epstein-Barr Virus Infections/etiology , Epstein-Barr Virus Infections/therapy , Humans , Leukemia, Large Granular Lymphocytic/virology , Male , Peripheral Blood Stem Cell Transplantation/methods , Recurrence , T-Lymphocytes, Cytotoxic/transplantation , Tissue Donors , Transplantation Chimera , Transplantation, Homologous
8.
Int J Clin Exp Pathol ; 7(1): 411-7, 2014.
Article in English | MEDLINE | ID: mdl-24427365

ABSTRACT

The patient was a 52-year old woman with a history of mosquito-bite hypersensitivity since childhood. In July 2011, she developed pyrexia, headaches, and nausea, and Epstein-Barr virus (EBV)-positive aggressive natural killer leukemia (ANKL) was diagnosed on the basis of both a peripheral blood and bone marrow examination. An inguinal lymph node biopsy, on the other hand, revealed EBV-positive cytotoxic T-cell lymphoma plus the presence of a small number of EBV-positive ANKL cells, and a diagnosis of EBV-positive composite lymphoma was made. Both the cytotoxic T-cell lymphoma and ANKL exhibited EBV terminal repeat (Southern blot analysis) monoclonal patterns, and they were almost the same size, approximately 9.0 kb. If it was the identical EBV clone, it is possible that EBV infected progenitor cells common to both NK cells and T cells, that the progenitor cells then differentiated into NK cells and T cells, a chronic active Epstein-Barr virus infection developed, and neoplastic transformation occurred. If it was not the identical EBV clone, fairly similar EBVs must have infected NK cells and T cells separately, and they then underwent neoplastic transformation. Because the mechanism by which EBV infects NK cells or T cells is still unknown, we concluded that this case is also important from the standpoint of elucidating it. We are currently in the process of conducting gene analyses to determine whether the fairly similar EBVs that infected the ANKL and cytotoxic T-cell lymphoma are the identical clone.


Subject(s)
Composite Lymphoma/pathology , Composite Lymphoma/virology , Epstein-Barr Virus Infections/complications , Leukemia, Large Granular Lymphocytic/pathology , Leukemia, Large Granular Lymphocytic/virology , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/virology , Epstein-Barr Virus Infections/pathology , Female , Flow Cytometry , Humans , Hypersensitivity/immunology , Insect Bites and Stings/immunology , Middle Aged
10.
Gan To Kagaku Ryoho ; 38(10): 1727-32, 2011 Oct.
Article in Japanese | MEDLINE | ID: mdl-21996977

ABSTRACT

There have been only three reports in the literature of T-cell large granular lymphocyte (T-LGL) leukemia occurring after autologous peripheral stem cell transplantation (APBSCT). We describe 3 patients in whom a transient monoclonal T-LGL developed after APBSCT for malignant lymphoma. Case 1: A 58-year-old man with peripheral T-cell lymphoma in second complete remission (CR) who underwent APBSCT. Case 2: A 51-year-old man with follicular lymphoma in second CR who underwent APBSCT. Case 3: A 65-year-old man with diffuse large B-cell lymphoma in second CR who underwent tandem APBSCT. One month after transplant, fever followed by the proliferation of CD8+/CD57+ T-LGL in peripheral blood occurred in all three cases. Because clonal rearrangements of the T-cell receptor were detected in peripheral blood samples, T-LGL leukemia was diagnosed. The first patient had episodes of Epstein-Barr virus viremia. The other patients suffered from cytomegalovirus colitis after APBSCT. These data show that T-LGL leukemia can occur after viral infection followed by APBSCT.


Subject(s)
Leukemia, Large Granular Lymphocytic/pathology , Lymphoma/surgery , Neoplasms, Second Primary/pathology , Peripheral Blood Stem Cell Transplantation , Aged , Cytomegalovirus/physiology , Herpesvirus 4, Human/physiology , Humans , Leukemia, Large Granular Lymphocytic/virology , Male , Middle Aged , Neoplasms, Second Primary/virology , Transplantation, Autologous
11.
Histopathology ; 59(4): 660-71, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22014047

ABSTRACT

AIMS: Extranodal natural killer (NK)/T-cell lymphoma (NKTL), comprising nasal NKTL and extranasal NKTL (ENKTL), is associated with Epstein-Barr virus (EBV). A bimodal age distribution was noted in NKTL patients. We examined the clinicopathological differences between two age groups of ENKTL patients (n = 23) and compared the findings with those of aggressive NK cell leukaemia (ANKL; n = 10) and monoclonal chronic active EBV infection-associated T/NK-cell lymphoproliferative disorders [chronic active EBV infection/TNK-lymphoproliferative disorders (CAEBV/TNK-LPD)] of NK-cell type (n = 45). METHODS AND RESULTS: Distinct differences existed between elderly (> 50 years; n = 13) and younger (≤ 50 years; n = 10) ENKTL patients; the latter showed a higher disease stage (P = 0.0286), worse performance status (P = 0.0244), more frequent B symptoms (P = 0.0286) and more frequent liver, spleen and bone marrow involvement (P = 0.0222, 0.0005 and 0.0259, respectively). Few clinicopathological differences existed between younger ENKTL and ANKL patients. Patients with monoclonal CAEBV/TNK-LPD of NK-cell type (n = 45) showed features similar to those in younger ENKTL/ANKL patients, except a more juvenile onset of CAEBV-related symptoms and better prognosis. However, the onset age of overt leukaemia/lymphoma in CAEBV/TNK-LPD patients and overall survival thereafter were similar to those in younger ENKTL/ANKL patients. CONCLUSIONS: ENKTL (≤ 50 years) is distinct from that in elderly patients and may encompass ANKL and overlap in the clinicopathological profile with NK-cell type CAEBV/TNK-LPD.


Subject(s)
Epstein-Barr Virus Infections/complications , Leukemia, Large Granular Lymphocytic/pathology , Lymphoma, Extranodal NK-T-Cell/pathology , Lymphoproliferative Disorders/pathology , Adolescent , Adult , Age Distribution , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Chronic Disease , Epstein-Barr Virus Infections/mortality , Epstein-Barr Virus Infections/pathology , Female , Humans , Immunophenotyping , Kaplan-Meier Estimate , Leukemia, Large Granular Lymphocytic/mortality , Leukemia, Large Granular Lymphocytic/virology , Lymphoma, Extranodal NK-T-Cell/mortality , Lymphoma, Extranodal NK-T-Cell/virology , Lymphoproliferative Disorders/mortality , Lymphoproliferative Disorders/virology , Male , Middle Aged , Neoplasm Staging , Young Adult
12.
Intern Med ; 49(17): 1907-10, 2010.
Article in English | MEDLINE | ID: mdl-20823655

ABSTRACT

Aggressive natural killer cell leukemia (ANKL) is a highly aggressive lymphoproliferative disease. An appropriate therapeutic strategy for ANKL remains to be established, but a few case reports have suggested that allogeneic hematopoietic stem cell transplantation (allo-HCT) can be curative. Here, we report a young woman with ANKL showing central nervous system (CNS) invasion, who has been in complete remission for more than a year after allo-HCT following two courses of intravenous chemotherapy and several rounds of intrathecal chemotherapy. Intensive remission induction chemotherapy followed by conventional myeloablative allo-HCT is a promising approach for long-term remission in cases of this aggressive malignancy.


Subject(s)
Leukemia, Large Granular Lymphocytic/surgery , Peripheral Blood Stem Cell Transplantation , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asparaginase/administration & dosage , Brain/pathology , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Doxorubicin/administration & dosage , Epstein-Barr Virus Infections/virology , Etoposide/administration & dosage , Female , Herpesvirus 4, Human/isolation & purification , Humans , Ifosfamide/administration & dosage , Injections, Spinal , Leukemia, Large Granular Lymphocytic/drug therapy , Leukemia, Large Granular Lymphocytic/virology , Leukemic Infiltration , Methotrexate/administration & dosage , Myeloablative Agonists/therapeutic use , Prednisone/administration & dosage , Radiography , Remission Induction , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/etiology , Transplantation Conditioning , Transplantation, Homologous , Vincristine/administration & dosage
13.
Blood ; 116(19): 3695-704, 2010 Nov 11.
Article in English | MEDLINE | ID: mdl-20671118

ABSTRACT

Therapeutic targeting of virus-encoded proteins using cellular immunotherapy has proved successful for Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. However, the more limited repertoire and immunogenicity of EBV-encoded proteins in other malignancies such as Hodgkin lymphoma and extranodal natural killer (NK)/T lymphoma has been more challenging to target. The immunosubdominant latent membrane protein 2 (LMP2) is considered the optimal target in such Latency II tumors, although data relating to its expression in T/NK malignancies are limited. In addressing the validity of LMP2 as an immunotherapeutic target we found that LMP2-specific effector CD8(+) T cells recognized and killed EBV-positive NK- and T-cell tumor lines, despite an apparent absence of LMP2A protein and barely detectable levels of LMP2 transcripts from the conventional LMP2A and LMP2B promoters. We resolved this paradox by identifying in these lines a novel LMP2 mRNA, initiated from within the EBV terminal repeats and containing downstream, epitope-encoding exons. This same mRNA was also highly expressed in primary (extra-nodal) NK/T lymphoma tissue, with virtually undetectable levels of conventional LMP2A/B transcripts. Expression of this novel transcript in T/NK-cell lymphoproliferative diseases validates LMP2 as an attractive target for cellular immunotherapy and implicates this truncated LMP2 protein in NK- and T-cell lymphomagenesis. This study is registered at clinicaltrials.gov as NCT00062868.


Subject(s)
Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/immunology , Leukemia, Large Granular Lymphocytic/immunology , Leukemia, Large Granular Lymphocytic/virology , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology , Base Sequence , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , DNA Primers/genetics , Epstein-Barr Virus Infections/therapy , Gene Expression , Genes, Viral , Herpesvirus 4, Human/pathogenicity , Humans , Immunotherapy, Adoptive , Killer Cells, Natural/immunology , Killer Cells, Natural/virology , Leukemia, Large Granular Lymphocytic/therapy , Lymphoma, Extranodal NK-T-Cell/immunology , Lymphoma, Extranodal NK-T-Cell/therapy , Lymphoma, Extranodal NK-T-Cell/virology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/virology
14.
AIDS Res Hum Retroviruses ; 26(1): 33-40, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20047475

ABSTRACT

Samples were obtained from 53 large granular lymphocytic leukemia (LGLL) patients and 10,000 volunteer blood donors (VBD). Sera were screened in an HTLV-1 enzyme immunoassay (EIA) and further analyzed in peptide-specific Western blots (WB). DNAs were analyzed by HTLV-1, -2, -3, and -4-specific PCR. Forty four percent of LGLL patients vs. 0.12 % of VBD had anti-HTLV antibodies via EIA (p < 0.001). WB and PCR revealed that four LGLL patients (7.5%) vs. one VBD patient (0.01%) were infected with HTLV-2 (p < 0.001), suggesting an HTLV-2 etiology in a minority of cases. No LGLL patient was positive for HTLV-1, -3, or -4, whereas only one EIA-positive VBD was positive for HTLV-1 and none for HTLV-3 or -4. The HTLV EIA-positive, PCR-negative LGLL patients' sera reacted to epitopes within HTLV p24 gag and gp21 env. Other then the PTLV/BLV viruses, human endogenous retroviral element HERV K10 was the only sequence homologous to these two HTLV peptides, raising the possibility of cross-reactivity. Although three LGLL patients (5.7%) vs. none of 110 VBD patients tested positive for antibodies to the homologous HERV K10 peptide (p = 0.03), the significance of the anti-HTLV seroreactivity observed in many LGLL patients remains unclear. Interestingly, out of 36 HTLV-1-positive control subjects, 3 (8%) (p = 0.014) were positive for antibodies to HERV K10; all three had myelopathy. Out of 64 HTLV-2-positive control subjects 16 (25%) (p = <0.001) were positive for HERV K10 antibodies, and 4 (6%) of these had myelopathy. Out of 22 subjects with either HTLV-1 or -2 myelopathy, 7 (31.8%) were positive for HERV K10 antibodies, and out of 72 HTLV-infected subjects without myelopathy, 12 (16.7%) were positive for anti-HERV K10 antibodies (p = 0.11). The prevalence of anti-HERV K10 antibodies in these populations and the clinical implications thereof need to be pursued further.


Subject(s)
HIV-2/isolation & purification , Human T-lymphotropic virus 1/isolation & purification , Human T-lymphotropic virus 2/isolation & purification , Human T-lymphotropic virus 3/isolation & purification , Leukemia, Large Granular Lymphocytic/virology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Viral/blood , Blotting, Western/methods , Cross Reactions , Endogenous Retroviruses/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , HIV-2/genetics , HIV-2/immunology , Human T-lymphotropic virus 1/genetics , Human T-lymphotropic virus 1/immunology , Human T-lymphotropic virus 2/genetics , Human T-lymphotropic virus 2/immunology , Human T-lymphotropic virus 3/genetics , Human T-lymphotropic virus 3/immunology , Humans , Leukemia Virus, Bovine/immunology , Male , Middle Aged , Polymerase Chain Reaction/methods , Seroepidemiologic Studies , Young Adult
15.
Pathol Res Pract ; 205(10): 730-4, 2009.
Article in English | MEDLINE | ID: mdl-19269751

ABSTRACT

We describe a patient who was diagnosed as having classic Hodgkin's lymphoma at 29 years of age, and aggressive natural killer-cell leukemia at 48 years. He died 42 days later. Hodgkin and Reed-Sternberg cells in the lymph node expressed CD30, CD15, T-cell intracellular antigen-1 (TIA-1), perforin, granzyme B, and Epstein-Barr virus-encoded RNA (EBER). Natural killer-cell leukemia cells in the bone marrow expressed cytoplasmic CD3epsilon, TIA-1, perforin, granzyme B, and EBER, and some neoplastic cells expressed CD56 (123C3). Fluorescence-activated cell sorter (FACS) analysis showed that neoplastic cells expressed CD56. Neither a rearrangement band of the T-cell receptor gene nor that of the immunoglobulin heavy chain gene was detected. Chromosomal abnormalities were noted.


Subject(s)
Epstein-Barr Virus Infections/complications , Hodgkin Disease/pathology , Leukemia, Large Granular Lymphocytic/pathology , Neoplasms, Second Primary/pathology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fatal Outcome , Flow Cytometry , Herpesvirus 4, Human , Hodgkin Disease/immunology , Hodgkin Disease/virology , Humans , Immunohistochemistry , Leukemia, Large Granular Lymphocytic/immunology , Leukemia, Large Granular Lymphocytic/virology , Male , Middle Aged , Neoplasms, Second Primary/immunology , Neoplasms, Second Primary/virology
17.
AIDS Res Hum Retroviruses ; 24(12): 1503-5, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19102684

ABSTRACT

Clonal disorders of large granular lymphocytes (LGL) result in leukemia due to the expansion of a discrete subset of either CD3(+) T cells or natural killer (NK) cells. It has been hypothesized that a viral antigen acts as the initial stimulus causing the expansion of these cells. The possible involvement of human T cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in this disease has been studied but no conclusive evidence has linked either virus with LGL leukemia. In this study, we examined whether HTLV-3 or HTLV-4, two newly identified HTLV groups discovered in Central Africa in primate hunters, is involved in LGL leukemia. We developed two specific real-time PCR quantitative assays that are highly sensitive, capable of detecting 10 copies of HTLV-3 or HTLV-4 pol sequences in a background of 1 microg of DNA from human peripheral blood lymphocytes (PBL). We tested PBL DNA samples from 40 LGL leukemia patients in the United States and found that all samples were negative for HTLV-3 or HTLV-4 infection. These results suggest that HTLV-3 and HTLV-4 are not the causative agent of LGL leukemia.


Subject(s)
HIV-2/isolation & purification , HIV/isolation & purification , Leukemia, Large Granular Lymphocytic/virology , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphocytes/virology , Male , Middle Aged , Polymerase Chain Reaction/methods , United States
18.
Am J Hematol ; 83(9): 721-7, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18626884

ABSTRACT

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation.


Subject(s)
Epstein-Barr Virus Infections/complications , Hematopoietic Stem Cell Transplantation , Lymphoproliferative Disorders/surgery , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Infant , Japan/epidemiology , Killer Cells, Natural/pathology , Leukemia, Large Granular Lymphocytic/epidemiology , Leukemia, Large Granular Lymphocytic/pathology , Leukemia, Large Granular Lymphocytic/surgery , Leukemia, Large Granular Lymphocytic/virology , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/surgery , Lymphoma, Non-Hodgkin/virology , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/epidemiology , Lymphoproliferative Disorders/pathology , Lymphoproliferative Disorders/virology , Male , Middle Aged , T-Lymphocytes/pathology , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome
19.
Int J Hematol ; 86(4): 348-51, 2007 Nov.
Article in English | MEDLINE | ID: mdl-18055343

ABSTRACT

A 60-year-old man was diagnosed with asymptomatic T-cell granular lymphocyte (T-LGL) leukemia in September 2006. He was serologically positive for human T-cell leukemia virus type 1 (HTLV-1). However, monoclonal integration of the HTLV-1 genome was not detected in the peripheral blood, suggesting that HTLV-1 did not contribute to the pathogenesis of T-LGL leukemia in the present case. Phenotypically, neoplastic cells of our case were CD3+, CD4*, CD8+, CD16-, CD56+, CD57*, and T-cell receptor (TCR) alphabeta+. They also coexpressed CD20 antigen with weak intensity. This represented a unique case of T-LGL leukemia showing a typical clinical and phenotypic features.


Subject(s)
Antigens, CD20/metabolism , CD56 Antigen/metabolism , Human T-lymphotropic virus 1/physiology , Leukemia, Large Granular Lymphocytic/metabolism , Leukemia, Large Granular Lymphocytic/virology , Flow Cytometry , Humans , Leukemia, Large Granular Lymphocytic/genetics , Leukemia, Large Granular Lymphocytic/pathology , Male , Middle Aged , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/metabolism
20.
Acta Haematol ; 101(4): 206-8, 1999.
Article in English | MEDLINE | ID: mdl-10436303

ABSTRACT

The conceptual view of natural killer (NK) cell malignancies has recently undergone a significant evolution. The majority of such diseases are associated with Epstein-Barr virus (EBV), while only a limited number of EBV-negative cases has been reported. We report an unusual case of NK cell lymphoma/leukemia showing a monomorphic histology, absence of intracytoplasmic azurophilic granules, and no EBV association. The patient was a 57-year-old woman who died 26 months after the diagnosis. Autopsy revealed tumor infiltration in the liver, spleen, lymph node, blood, and bone marrow. There was no involvement of the skin or nasal cavity throughout the clinical course. The tumor showed the monotonous proliferation of medium-sized cells without intracytoplasmic azurophilic granules. Phenotypic analysis showed CD2+, CD3/Leu4-, cytoplasmic CD3epsilon+, CD4-, CD5-, CD7+, CD8-, CD16-, CD38+, CD56+, CD57-, TdT-, granzyme B-, and TIA1+ phenotype. There were no detectable rearrangements of T cell receptor genes or immunoglobulin heavy chain genes. Furthermore, there were no EBV-encoded small RNAs. These findings provide information to improve the understanding of poorly defined entities, i.e. aggressive NK cell lymphoma/leukemia and blastic NK cell lymphoma/leukemia.


Subject(s)
Herpesvirus 4, Human/isolation & purification , Killer Cells, Natural/pathology , Leukemia, Large Granular Lymphocytic/pathology , Lymphoma/pathology , Colonic Neoplasms/diagnosis , Fatal Outcome , Female , Humans , Immunophenotyping , Killer Cells, Natural/virology , Leukemia, Large Granular Lymphocytic/virology , Lymphoma/virology , Middle Aged , Neoplasms, Second Primary/diagnosis
SELECTION OF CITATIONS
SEARCH DETAIL
...