Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kaposi's varicelliform eruption is characterized by disseminated vesiculopustules and erosions caused by a herpes virus infection superimposed on a pre-existing dermatosis. The eruption usually occurs in individuals with atopic dermatitis or other pre-existing dermatosis such as Darier's disease, pemphigus foliaceus, mycosis fungoides, Sezary syndrome, benign familial pemphigus, ichthyosis vulgaris, second-degree burns, multiple myeloma, and Grover's disease. We report here a new case of Kaposi's varicelliform eruption in a 38-year-old woman with rosacea. To our knowledge, this is the first case of Kaposi's varicelliform eruption associated with rosacea to be reported.
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PMID:Kaposi's varicelliform eruption in association with rosacea. 1557 62

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.
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PMID:Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. 1557 69

The ubiquitin-proteasome pathway is responsible for degrading many critical regulatory proteins involved in immune and inflammatory responses, control of cell growth and apoptosis. Recently, proteasome inhibitors have emerged as promising new therapeutic agents in hematological malignancies. Here we show that Bortezomib (PS-341), a proteasome-inhibitor, inhibits cellular proliferation and induces apoptosis in cell lines derived from Primary Effusion Lymphoma (PEL), a subtype of non-Hodgkin's lymphoma associated with infection by human herpes virus 8 (HHV-8). Bortezomib demonstrated more cytotoxicity against PEL cells than against cell lines derived from multiple myeloma, a disease for which is in current clinical use. Apoptosis induced by Bortezomib was associated with inhibition of the classical and alternative NF-kappaB pathways, upregulation of p53, p21 and p27 and activation of caspase cascade. Finally, treatment of PEL cells with Bortezomib exerted a synergistic or additive cytotoxic effect in combination with chemotherapeutic drugs or TRAIL. Taken together, these findings suggest that Bortezomib represents a promising agent for the treatment of PEL.
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PMID:The proteasome inhibitor bortezomib (PS-341) inhibits growth and induces apoptosis in primary effusion lymphoma cells. 1590 93

The aim of this study was to assess the side effects and the efficacy of thalidomide alone or in combination with dexamethasone in relapsed multiple myeloma (MM) and to evaluate possible predictive factors for response rate and survival. Twenty-nine pretreated patients were enrolled, including 13 patients with a relapse after high-dose chemotherapy. The median number of relapses was 3 (range: 1-7). Twenty-two patients received thalidomide in combination with dexamethasone and seven patients thalidomide alone. The dosage of thalidomide was 400 mg/day and the dosage of dexamethasone 20 mg/m2 daily for 4 consecutive days every 3 weeks. Cycles of dexamethasone were given until maximal decline of myeloma protein was achieved, whereas therapy with thalidomide was maintained until disease progression. Responses occurred in 62% of patients, including 5 (17%) complete remissions and 13 (45%) partial remissions. The median event-free survival (EFS) was 7.2 months and the median overall survival (OS) 26.1 months. In multivariate analysis, pretreatment serum levels of soluble interleukin-2 receptor (sIL-2R) were a significant prognostic factor for EFS, and those of beta2-microglobulin (beta2M) and sIL-2R for OS. Serum levels of sIL-2R significantly increased after 3 weeks of treatment in 89% of patients, possibly representing lymphocyte activation induced by thalidomide. Two patients died of septic complications within 3 months after starting treatment with thalidomide and dexamethasone and one patient of herpes encephalitis after 26 months of treatment with thalidomide alone. Also, one case of pneumonia and one case of deep venous thrombosis of the lower limb occurred. Other side effects were somnolence, peripheral neuropathy, and bradycardia occurring in 35, 55, 38 and 55% of patients, respectively. The combination of thalidomide and dexamethasone is an effective therapy in heavily pretreated myeloma patients with a high response rate and acceptable toxicities. A powerful predictive factor both for EFS and OS was the pretreatment serum level of sIL-2R.
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PMID:Thalidomide in combination with dexamethasone for pretreated patients with multiple myeloma: serum level of soluble interleukin-2 receptor as a predictive factor for response rate and for survival. 1574 24

Cancer incidence is increased in renal transplant recipients due to immunosuppressant treatment that should be maintained to prevent and treat acute rejection. Use of new and very potent immunosuppressants has made it possible to reduce acute rejection incidence and improve renal graft survival, although increase of infections and post-transplant neoplasms have become clearer. On the other hand, renal transplant candidates who remain on dialysis have a greater prevalence of neoplasms than the age-matched general population, either because the neoplasm was the cause of their renal failure (multiple myeloma or kidney or urinary tract cancers) or because their renal disease entails a risk for cancer development (acquired cystic disease or analgesic nephropathy). Practically, all de novo neoplasms have a greater incidence in renal transplant patients. Cutaneous neoplasms are the most prevalent in renal transplant recipients and their incidence increases with transplant time. Post-transplant lymphoproliferative diseases are more frequent in patients who receive greater immunosuppression (antithymocyte/antilymphocyte globulin or OKT3) or are infected de novo by Epstein Barr Virus (EBV) through the transplanted kidney. Kaposi's sarcoma has a high incidence in the renal transplanted population, does not appear in the general population, and is related with Human Herpes Virus 8 (HHV-8) infections. The incidence of tumors in non-functioning native kidneys is especially high in renal transplant due to the presence of acquired cystic disease or analgesic nephropathy. Gold standards of post-transplant de novo renal neoplasm prevention are modulating immunosuppression and avoiding exposure to sunlight and to different oncogenic viruses (EBV, cytomegalovirus, hepatitis B and C viruses).
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PMID:Cancer incidence after immunosuppressive treatment following kidney transplantation. 1597 27

AIDS-associated aggressive B-cell lymphomas often have plasmacytoid features. Plasma cell neoplasms in HIV patients were commonly described to have atypical morphology and an aggressive clinical course in the literature. We reviewed 14 cases of neoplasms with marked plasmacytic differentiation in HIV-positive patients to determine their clinicopathologic features. Of these, 13 of 14 had homogeneous morphology and were generally CD45(+), CD20-, PAX-5-, and CD138(+). All were positive for Epstein-Barr virus-encoded RNA (EBER) but lacked EBV late membrane proteins (LMP). Human herpes virus 8 (HHV8) DNA was detected in 6 of 10 cases by nested PCR, but HHV8 latent nuclear antigen (LNA) was absent. The 13 patients ranged in age from 28 to 44 years (median, 41 years) (11 male patients; 2 female patients). All patients had extramedullary and 11 of 13 had extranodal tumor at the initial presentation; 2 had distant marrow involvement. The most commonly involved location was the oral cavity (6 of 13 cases), followed by bone and soft tissue (4 of 13), and the gastrointestinal tract (3 of 13). All 11 patients with follow-up died within 34 months (median, 7 months). The 14th patient who had a nodal disease with more undifferentiated morphology and expression of the HHV8 LNA protein was alive without disease at last follow-up (>72 months), probably representing a novel HHV8(+) lymphoma. We conclude that most plasmacytic tumors in HIV-positive individuals are extramedullary, clinically aggressive EBV(+) tumors identical to plasmablastic lymphoma that does not have the clinical features of plasma cell myeloma.
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PMID:Plasmablastic lymphoma in HIV-positive patients: an aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm. 1632 36

Communicable respiratory viruses as a causative factor of infectious complication in hemoblastosis and myelodepression were investigated in 51 patients (aplastic anemia--3, multiple myeloma--10, different patterns of acute leukemia--16, chronic leukemia--8 and non-Hodgkin's lymphoma--14). Our clinical evidence obtained with the aid of polymerase chain reaction featured genomes of adenoviruses, influenza A and B viruses, respiratory-scintillating virus and coronaviruses. On the whole, respiratory viral infections were detected in 27 (52.9%) patients: adenoviruses--23.5%, coronaviruses--13.7%, influenza A and B--5.9% and respiratory-scintillating virus--3.9%. In many cases, herpes was associated with viral respiratory infection. That pathology was most often triggered by severe neutropenia induced by chemotherapy.
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PMID:[Molecular biology investigation of respiratory viruses as a factor of infectious complications in hemoblastosis and myelodepression]. 1702 15

Plasmablastic microlymphoma (PML) is defined as the accumulation of monotypic but polyclonal plasmablasts in lymphoid tissues involved in human herpes virus 8 (HHV-8)-positive multicentric Castleman's disease (MCD). So far, the nature of this very rare condition remains poorly determined. In this study, we describe a human immunodeficiency virus (HIV)-seropositive patient who developed a PML in the setting of HHV-8-positive MCD. In contrast to the cases previously reported, most of the plasmablasts in our patient were localized within the germinal center (GC) of lymphoid follicles. These plasmablasts expressed the multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) protein as well as IgMlambda in a monotypic fashion. They did not show any immunoreactivity with antibodies directed against Pax-5, CD20, CD79a, CD10, CD30, CD23, CD138, epithelial membrane antigen (EMA) or BCL-6. These cells exhibited a high proliferation rate, expressed the HHV-8 latent nuclear antigen-1, and secreted the HHV-8 viral homologue of human interleukin-6. Polymerase chain reaction analysis did not demonstrate any clonal rearrangement of the genes coding for the heavy chain of the immunoglobulin. Moreover, no Epstein-Barr virus (EBV) RNA transcript could be found, using in situ hybridization. The present case illustrates that PML may arise within the GC of lymphoid follicles in the absence of EBV coinfection. In our opinion, PML occurring in MCD likely represents a variant of HHV-8-positive MCD in which lytic HHV-8 replication is particularly prominent, due to a local or systemic immune imbalance.
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PMID:Plasmablastic microlymphoma occurring in human herpesvirus 8 (HHV-8)-positive multicentric Castleman's disease and featuring a follicular growth pattern. 1761 57

We report on bone marrow plasmacytosis in four cases of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL). Pathologically, the plasma cells increased in number and accounted for 20-40% of nucleated cells of bone marrow. These plasma cells diffusely infiltrated or formed numerous clusters with 50-200 cells on histological sections. Some binuclear plasma cells and Russell bodies were seen, but all plasma cells showed mature cytomorphology. One case contained two lymphoid follicles with normal germinal centers. Immunoperoxidase studies of light chain determinants for plasma cells and their precursors demonstrated a polyclonal pattern. The immunohistochemical study revealed that there were no human herpes virus-8-positive cells. Bone marrow plasmacytosis of striking proportions may occur in a number of inflammatory conditions, chronic infections, autoimmune diseases, and hypersensitivity states. These reactive plasmacytoses, although sometimes striking, are generally composed of scattered, non-aggregated plasma cells. The four cases described here contained numerous tumor-like aggregations on mature plasma cells. Our four cases should be differentiated from plasma cell myeloma composed of mature plasma cells. However, electrophoresis generally demonstrated a broad-based polyclonal hypergammmaglobulinemia. Moreover, the immunohistochemical study revealed a polytypic nature of the plasma cells. To avoid overdiagnosis and overtreatment, it is important to be aware of the bone marrow findings of IPL.
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PMID:Bone marrow plasmacytosis in idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia: a report of four cases. 1790

Infections continue to be a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), as therapeutic advances have occurred over the past several decades. The pathogenesis of infection in these patients is multifactorial, including inherent immune defects related to the primary disease process, such as hypogammaglobulinemia, as well as therapy-related immunosuppression. A characteristic spectrum of infectious complications has been described for specific treatment agents. With chlorambucil, most infections are bacterial in origin, caused by common Gram-positive and -negative organisms. Recurrent infections are a hallmark, with the respiratory tract being the most common site of infection. The pathogenesis of infection with the purine analogues is related to the quantitative and qualitative T-cell abnormalities induced by these agents. Risk factors for infection identified in patients treated with fludarabine include advanced-stage disease, prior CLL therapy, response to therapy, elevated serum creatinine, hemoglobin < 12 g/dL, and decreased serum IgG. As compared with patients receiving chlorambucil, patients receiving fludarabine have more major infections and herpes virus infections. However, Pneumocystis, Aspergillus, and cytomegalovirus (CMV) infections are uncommon. The use of alemtuzumab is complicated by frequent opportunistic infections. CMV reactivation is especially problematic, occurring in 10%-25% of patients. For prevention of infection, the use of vaccinations and immunoglobulin replacement has been studied. Recommendations for prophylactic antimicrobial therapy have arisen from CLL treatment trials and anecdotal reports. As new treatment approaches are developed for CLL, one must consider not only the efficacy of these agents for disease response but also the effect on subsequent infectious complications. Infectious complications remain a significant cause of morbidity and mortality in patients with CLL. We will review the pathogenesis as well as the spectrum of infections in these patients. We will also discuss approaches to the prophylactic and therapeutic management of infections in these patients.
Clin Lymphoma Myeloma 2009 Oct
PMID:Infectious complications in patients with chronic lymphocytic leukemia: pathogenesis, spectrum of infection, and approaches to prophylaxis. 1985 55


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