Biomarkers ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; metabolism ; Cytomegalovirus Retinitis ; immunology ; Female ; Humans ; Male ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; metabolism ; virology

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.
Animals ; Basic-Leucine Zipper Transcription Factors ; genetics ; metabolism ; Carcinogenesis ; HTLV-I Infections ; pathology ; virology ; Human T-lymphotropic virus 1 ; genetics ; metabolism ; Humans ; Leukemia, T-Cell ; pathology ; virology ; Retroviridae Proteins ; genetics ; metabolism

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of leukemia patients can improve overall survival and disease-free survival, and reduce relapse. Although the allo-HSCT is more widely used in the treatment of leukemia, but the graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infections are the common complications, and are the major cause of mortality for patients following allo-HSCT. Previous studies showed that there might be a mutual promotive relationship between GVHD and CMV infection, but the clear relationship remained to be elucidated. The relationship of GVHD and CMV has been the focus of clinical research. Recently, a great progress has been made on researches of the relationship and its mechanism between GVHD and CMV infection. In this article, the relationship and its mechanism between GVHD and CMV infection after allo-HSCT are reviewed.
Cytomegalovirus Infections ; complications ; Disease-Free Survival ; Graft vs Host Disease ; complications ; virology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Leukemia ; therapy ; Recurrence

Female ; Hepatitis C ; complications ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Interferons ; therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; complications ; drug therapy ; virology ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Treatment Outcome

OBJECTIVETo explore the characteristics and risk of etoposide-related leukemia in the treatment of hemophagocytic lymphohistiocytosis (HLH).

METHODClinical characteristics of a case with secondary acute promyelocytic leukemia (APL) were summarized and 10 cases of secondary leukemia after treatment for HLH from literature were analyzed.

RESULTThe child was diagnosed with Epstein-Barr virus associated HLH and received HLH-2004 protocol. The cumulative dose of etoposide (VP16) was 3520 mg/m(2). The patient was diagnosed with APL after 28 months of HLH.He achieved complete remission after induction chemotherapy of all-trans-retinoic acid and darubicin. Consolidated chemotherapy was continued. There were 10 reports of etoposide-related leukemia after treatment for HLH in the literature.Review of 11 cases treated with VP16, of which cumulative doses were 900-20 500 mg/m(2). The interval period between HLH and secondary leukemia was 24 months. The types of secondary leukemia included 1 case with acute lymphoblastic leukemia, 1 case with myelodysplastic syndrome and 9 cases of acute myeloid leukemia. The abnormalities of chromosome included 3 patients with 11q23, 3 APL patients with t (15, 17).Seven patients survived and 4 died.

CONCLUSIONThe latency period of etoposide-related leukemia is short. Acute myeloid leukemia and balanced chromosomal abnormality are common in etoposide-related leukemia. The risk factors for development of secondary leukemia are related to cumulative drug doses of etoposide, treatment schedules and co-administration of other antineoplastic agents.It is appropriate to keep suitable range of the cumulative dose of etoposide in HLH therapy in order to reduce the risk of therapy related leukemia.

Acute Disease ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child, Preschool ; Daunorubicin ; administration & dosage ; Epstein-Barr Virus Infections ; complications ; drug therapy ; virology ; Etoposide ; administration & dosage ; adverse effects ; Humans ; Leukemia, Promyelocytic, Acute ; chemically induced ; drug therapy ; Lymphohistiocytosis, Hemophagocytic ; complications ; drug therapy ; virology ; Male ; Neoplasms, Second Primary ; chemically induced ; Risk Assessment ; Treatment Outcome ; Tretinoin ; administration & dosage

OBJECTIVETo investigate the associations between Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) infections and the methylation levels of PTEN and hTERT genes and explore their roles in children with acute lymphoblastic leukemia (ALL).

METHODSBlood samples from 100 children with newly diagnosed acute lymphoblastic leukemia were centrifuged for serological detection of EBV and HCMV, and the patients were divided accordingly into EBV-infected group (n=20), HCMV-infected group (n=14), EBV and HCMV co-infected group (n=41), and non-infected group (control group, n=15). DNA was extracted from peripheral blood mononuclear cells (PBMCs) and modified with bisulfite ammonia sodium. The methylation levels of the promoters of PTEN and hTERT genes were detected with methylation-specific polymerase chain reaction (MS-PCR).

RESULTSCompared with those in non-infected group and EBV- or HCMV-infected group, the methylation levels of PTEN gene in the co-infected group were significantly decreased (P<0.05) while the methylation levels of hTERT gene significantly increased (P<0.05).

CONCLUSIONIn children with acute lymphoblastic leukemia, EBV and HCMV co-infection cause changes in the methylation levels of PTEN and hTERT. These results may be associated with epigenetic changes caused by viral infections, and further studies are needed to further verify this hypothesis.

Child ; Coinfection ; Cytomegalovirus ; isolation & purification ; Cytomegalovirus Infections ; DNA Methylation ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; isolation & purification ; Humans ; PTEN Phosphohydrolase ; genetics ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; genetics ; virology ; Promoter Regions, Genetic ; Telomerase ; genetics ; metabolism

Imatinib mesylate is a molecular targeted agent for treating chronic myeloid leukemia (CML) and gastrointestinal stromal tumor. Although imatinib mesylate is not regarded as an immunosuppressive agent, few studies have also shown that it may impair immune response. In this report, we present a case of transient hepatitis B virus (HBV) reactivation during imatinib mesylate treatment for CML.
Adult ; Benzamides ; Hepatitis B virus ; pathogenicity ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; virology ; Male ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Virus Replication ; drug effects

OBJECTIVETo probe the cause for triggering HBV reactivation and possible management of the chronic hepatitis B individuals received imatinib.

METHODSThis study presented two cases of transient hepatitis B virus (HBV) reactivation and hepatic dysfunction during oral imatinib for chronic myeloid leukemia (CML) and made a literatures review about the pathogenesis, possible prophylactic and therapeutic management of such chronic hepatitis B individuals receiving imatinib.

RESULTSTwo CML patients, without prior liver dysfunction but with chronic HBV infection, suffered from transient HBV reactivation occurred during oral imatinib. Both of them finally obtained good outcome following the additional oral nucleotide antiviral therapy.

CONCLUSIONIt remained unclear whether imatinib induced the reactivation of HBV in patients with a latent HBV infection. From our study, all candidates receiving oral imatinib should be screened for HBsAg and anti-HBc antibodies prior to initiation of imatinib. Prophylactic antiviral therapy should be offered to HBV-infected individuals along with a close monitoring for signs of reactivation.

Adult ; Benzamides ; adverse effects ; therapeutic use ; Hepatitis B ; virology ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; virology ; Male ; Piperazines ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Virus Activation ; drug effects

OBJECTIVETo study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD).

METHODSThe clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues.

RESULTSAmongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease.

CONCLUSIONSThe diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.

ADP-ribosyl Cyclase 1 ; metabolism ; Adolescent ; Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antigens, CD20 ; metabolism ; Antineoplastic Agents ; therapeutic use ; Child ; Epstein-Barr Virus Infections ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunosuppressive Agents ; therapeutic use ; Ki-1 Antigen ; metabolism ; Kidney Transplantation ; adverse effects ; Leukemia ; therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; etiology ; pathology ; virology ; Lymphoproliferative Disorders ; drug therapy ; etiology ; pathology ; virology ; Male ; Middle Aged ; RNA, Viral ; metabolism ; Retrospective Studies ; Rituximab ; Young Adult

Human T cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T cell leukemia and lymphoma (ATL), infects over 20 million people worldwide. About 1 million of HTLV-1-infected patients develop ATL, a highly aggressive non-Hodgkin's lymphoma without an effective therapy. The pX region of the HTLV-1 viral genome encodes an oncogenic protein, Tax, which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression. Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis. Tax exhibits diverse functions in host cells, and this oncoprotein primarily targets IκB kinase complex in the cytoplasm, resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression. We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity. We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways. Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.
Autophagy ; CD4-Positive T-Lymphocytes ; metabolism ; virology ; Cell Cycle ; Cell Transformation, Neoplastic ; genetics ; Gene Expression Regulation, Neoplastic ; Gene Products, tax ; genetics ; metabolism ; Human T-lymphotropic virus 1 ; physiology ; Humans ; I-kappa B Kinase ; genetics ; metabolism ; Leukemia-Lymphoma, Adult T-Cell ; genetics ; metabolism ; virology ; Membrane Microdomains ; metabolism ; virology ; NF-kappa B ; genetics ; metabolism ; Protein Binding ; Signal Transduction ; genetics