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

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.
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PMID:Expression patterns of costimulatory molecules on cells derived from human hematological malignancies. 989 58

ICSAT (Interferon Consensus Sequence binding protein for Activated T cells) is a lymphocyte-specific member of the interferon regulatory factor (IRF) family of transcription factors, originally identified through Southwestern screening of the ATL(Adult T-cell leukemia)-16T expression library. In this study, we created transgenic mice overexpressing ICSAT in lymphocytes. Although spontaneous tumorigenesis was not observed, IL-2 production with Concanavalin A stimulation was significantly increased in transgenic mice overexpressing ICSAT. ICSAT overexpression in lymphocytes seems insufficient for the leukemogenesis of ATL or multiple myeloma (MM), however, it may regulate T cell activation and its overexpression may lead to leukemogenesis via controlling IL-2 production.
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PMID:ICSAT overexpression is not sufficient to cause adult T-cell leukemia or multiple myeloma. 1040 70

MUM1/IRF4 is a myeloma-associated oncogene transcriptionally activated as a result of t(6;14)(p25,q32) chromosomal translocation and by virtue of its juxtaposition to the immunoglobulin heavy chain gene (IgH) locus. When this oncogene becomes non-functional, no activated B/T lymphocytes and Ig secreting plasma cells are observed, suggesting that MUM1/IRF4 is crucial for lymphoid development. Its expression was analyzed in both reactive lymphoid and lymphoma tissues by means of an immunohistochemical technique using specific goat antiserum against MUM1/IRF4. This analysis detected a 50 kDa MUM1 product whose localization was restricted to the nuclei of the lymphocytes. The MUM1+ cells in reactive lymph nodes were found to consist of plasma cells and a small fraction (approximately 7.9%) of B cells harboring CD20+CD38+, which were located in the light zone of the germinal center. MUM1 expression in peripheral blood B/T lymphocytes was upregulated by mitogenic stimuli, suggesting that MUM1 positivity represents the activated state of the B/T cells. In B cell non-Hodgkin's lymphoma (NHL), MUM1 expression was observed in 73.2% (30/41) of diffuse large B cell lymphoma (DLBCL), 20% (1/5) of marginal zone lymphoma (MZL) and 43% (3/7) of small lymphocytic lymphoma (SLL) cases, whereas it was not seen in any cases of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL). Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases. Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.
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PMID:MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies. 1072 Jan 41

Bone involvement is a rare event in lymphomas, except in patients with adult T-cell leukemia/lymphoma associated with HTLVI. It is usually characterised by lytic bone lesions located in the metaphysis of long bones or in the axial skeleton. The occurrence of bone lesions reflects a progression of the disease affecting the prognosis that is related to lymphoma histologic features and staging. Bone lesions may occur in some lymphoproliferative disorders such as LLC or Waldenstrom's disease, or in myeloproliferative disorders. They may reflect a progression to a more aggressive disorder with a worse prognosis. The treatment of hematologic malignancies presenting with bone lesions and/or hypercalcemia is similar to the treatment of the systemic disease. In primary lymphomas of bone presenting with an isolated bone lesion, local treatment with radiation therapy and/or surgical ablation is required, and adjuvant chemotherapy may improve the prognosis of these located lymphomas. Glucocorticoid therapy and bisphosphonates are effective in treating associated hypercalcemia. Except for myeloma and ATL, the underlying mechanisms responsible for bone involvement in hematologic malignancies remain poorly understood. The unusual occurrence of bone lesions in these diseases probably implies distinct pathogenic mechanisms, but one can speculate that an increased expression of RANK/RANKL, the common final pathway in bone resorption, may be involved.
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PMID:Hematological malignancies and the bone (myeloma excluded). 1096 72

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.
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PMID:The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists. 1101 82

A novel therapeutic potential for acute promyelocytic leukemia using arsenic trioxide (As(2) O(3) ) has been reported. Recent in vitro studies demonstrated that As(2) O(3) effectively inhibits the growth of some cell lines derived from patients with malignant lymphoma, chronic lymphocytic leukemia and multiple myeloma. Adult T-cell leukemia (ATL) is an aggressive neoplasm of mature T-cell origin caused by human T-cell leukemia virus type-I (HTLV-I) the prognosis of which still remains very poor. A possible role of As(2) O(3) for the treatment of ATL is demonstrated from evidence that As(2) O(3) significantly inhibits the growth of HTLV-I infected T-cell lines and induces apoptosis in fresh ATL cells at clinically achievable concentration of the agent. The growth inhibition of As(2) O(3) treated HTLV-I infected T-cell lines was induced by both apoptosis and G(1) phase accumulation. Cleaved bcl-2 protein and an enhanced expression of bak protein in the cells were coincidentally observed during As(2) O(3) treatment. A broad spectrum caspase inhibitor, z-Val-Ala-DL-Asp-fluoromethylketone inhibited the apoptosis induced by As(2) O(3). Increased expression of p53, Cip1/p21 and Kip1/p27, and dephosphorylation of retinoblastoma protein (pRb) were detected in the As(2) O(3) treated cells. In conclusion, As(2) O(3) might become a new therapeutic tool in the treatment of ATL as As(2) O(3) induces apoptosis by destruction of the bcl-2 protein and enhancement of the bak protein production proceeding to activate caspases, and also induces G(1) phase accumulation by enhancement of p53, Cip1/p21, Kip1/p27 and dephosphorylation of pRb to HTLV-I infected T-cell lines.
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PMID:Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines. 1104 29

A registry of hematological malignancies is held in the unit of cytology of the University Hospital of Martinique. Human T cell lymphotropic virus type-1 (HTLV1) is endemic in this island. We determined the incidence and epidemiological features of hematological malignancies from the 715 new cases diagnosed between 1990 and 1998 among the adult population. Incidence rates per year were steady during this period. The most frequent hematological malignancies were multiple myeloma (MM) (34%), followed by non-Hodgkin's lymphoma (NHL) (23%). Among the cases of NHL with an immunohistological study, 57% had a T cell phenotype. Among these 61% were adult T cell leukemia/lymphoma. Epidemiological data on hematological malignancies in the West Indies has not been previously reported. There are two striking differences with other population-based registries: a high incidence of MM (5/100000) and a high proportion of T cell NHL among NHL (57%). The high proportion of T cell NHL is probably due to the high incidence of ATL. A low incidence of B cell NHL might also contribute to this effect. The increased incidence of MM in West Indies had not been previously reported. A similar high incidence of MM has been reported among Afro-Americans in the USA.
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PMID:Incidence of hematological malignancies in Martinique, French West Indies, overrepresentation of multiple myeloma and adult T cell leukemia/lymphoma. 1136 45

Adult T-cell leukemia (ATL) is endemic in southwestern Japan, in the Caribbean islands, and in central Africa. Human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of ATL. The clinical characteristics are (1) onset in adulthood, (2) subacute or chronic leukemia with rapidly progressive terminal course, (3) frequent skin lesions, (4) lymphadenopathy that characteristically spares the mediastinum, (5) hepatosplenomegaly, (6) hypercalcemia, and (7) a tendency toward geographical clustering. Although hypercalcemia and osteoclastic activity due to parathyroid hormone-related peptide are frequently reported histologically, radiographic abnormalities of bone are not common. Two major patterns of osteolytic lesions observed in ATL are "punched-out" lesions resembling multiple myeloma and osteolytic metastasis and subperiosteal bone resorptions similar to those in hyperparathyroidism.
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PMID:Adult T-cell leukemia. 1150 Jan 47

The Kyushu Hematology Organization for Treatment (K-HOT) Study Group was organized in 1999 to study hematological disorders diagnosed in the participating institutions in the Kyushu district. We registered all new patients with hematological disorders and from February 2000 to the end of 2003, a total of 2908 patients had been registered. They include non-Hodgkin's lymphoma in 803 patients, leukemia in 556, multiple myeloma (MM) in 276, myelodysplastic syndrome in 273, and adult T-cell leukemia/lymphoma (ATL) in 269 followed in a decreasing order by idiopathic thrombocytopenic purpura, aplastic anemia, and other benign hematological disorders and myeloproliferative disorders. The annual incidence of MM is estimated to be much higher than that previously reported. It is also confirmed that ATL is still one of the frequently encountered lymphoid malignancies in the Kyushu district.
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PMID:[Registration of hematological disorders by the Kyushu Hematology Organization for Treatment (K-HOT) Study Group]. 1528 25

Among the hematological malignancies, hypercalcemia has often been reported in lymphoid malignancies such as multiple myeloma and adult T cell leukemia/lymphoma, but it has only rarely been described in acute nonlymphocytic leukemia. We describe here a 14-month-old girl with acute monocytic leukemia complicated by severe hypercalcemia (4.6 mmol/l) at presentation. A bone survey showed generalized bone resorption, but no localized osteolytic lesions. A search for the etiology of the hypercalcemia revealed that the serum levels of parathyroid hormone-related protein (PTHrP) and also proinflammatory cytokines with stimulatory effects on osteolytic bone resorption - TNF-alpha, IL-6 and M-CSF - were elevated. The patient achieved complete remission with induction chemotherapy, and the levels of PTHrP and the cytokines became normalized. In this case, PTHrP and cytokines might have acted cooperatively to exacerbate bone resorption, resulting in severe hypercalcemia.
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PMID:Severe hypercalcemia in a child with acute nonlymphocytic leukemia: the role of parathyroid hormone-related protein and proinflammatory cytokines. 1534 99


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