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)

Multiple myeloma of IgG kappa type was diagnosed in a 42-year-old man with bone pains, dyspnoea on exertion and increasing drowsiness. Six chemotherapy cycles extending over 14 weeks and consisting of 15 mg/m2 melphalan intravenously on day 1 and 60 mg/m2 prednisolone orally on days 1-4 produced a partial remission. As the HLA-identical sister of the patient was willing to donate bone marrow, an allogeneic marrow transplantation was planned. After 7 days' conditioning treatment (hyperfractionated whole-body irradiation with 12 Gy, chemotherapy with 70 mg/m2 melphalan and 60 mg/kg cyclophosphamide), 4.2 x 10(8) nucleated cells of donor marrow were infused per kg recipient body-weight through a central venous catheter. Despite prophylaxis with short-course methotrexate and cyclosporin, an acute graft-versus-host reaction of grade II-III occurred on day 26, though it settled almost completely after treatment with daily 2 mg/kg prednisone and monoclonal interleukin-2 receptor antibodies (B-B10, daily 10 mg). On day 100 after the marrow transplantation, marrow puncture showed the picture of complete remission with normal regeneration of haemopoietic cells. Allogeneic marrow transplantation may therefore be considered as a new and promising mode of treatment for younger patients with multiple myelomas.
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PMID:[Therapy of multiple myeloma by allogeneic bone marrow transplantation]. 190 93

We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70-75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody (MoAb), designated Mik-beta 1, which has been recently developed. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis. These results indicate that flow cytometric analysis using MoAbs, anti-Tac, and Mik-beta 1 is useful for detecting the expression of the IL-2R chains.
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PMID:Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells. 238 56

Levels of the soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 69 patients with plasma cell dyscrasias. A close relationship was seen between serum sIL-2R levels and clinical features. Among patients with normal BUN and creatinine levels, the mean (+/- 1SD) level of sIL-2R in 44 patients with multiple myeloma (MM) was higher than that of normal controls (457 +/- 227 U/ml vs 288 +/- 124 U/ml, P = 0.01). The mean level of sIL-2R in eight patients with primary macroglobulinemia was 722 +/- 251 U/ml. In MM, those with active or refractory disease showed a significantly higher mean level of sIL-2R than those in the remission phase (577 +/- 240 U/ml vs 335 +/- 103 U/ml, P = 0.01). There was a negative correlation between sIL-2R and hemoglobin levels in MM patients (r = -0.45, P = 0.01). Five patients with complications of renal insufficiency had elevated levels of sIL-2R. In a longitudinal study of a patient with plasmacytoma and an extremely high sIL2-R level, the sIL-2R level showed a strong relationship with tumor burden. Patients with high sIL-2R levels generally had a poor prognosis than those with normal levels. Thus a high sIL-2R level may be an indicator of a poor prognosis in MM.
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PMID:Soluble interleukin-2 receptors in plasma cell dyscrasias. 261 49

Anti-Tac is a monoclonal antibody that appears to recognize the interleukin-2 receptor. With the use of a frozen-section immunoperoxidase technic, a large series of non-Hodgkin's lymphomas were investigated for the presence of Tac-antigen on neoplastic cells. Approximately one-fourth of cases expressed the Tac antigen, including 27% of B-lineage lymphomas, 6% of the T-lineage lymphomas, and three of four cases of Ki-1-expressing lymphoma. The B-lineage lymphomas with the highest incidence of Tac antigen expression were the large cell lymphomas, both diffuse and follicular, where about one-half of cases expressed the Tac antigen. All major categories of lymphoma expressed Tac except plasma-cytoma/myeloma, small noncleaved cell (Burkitt's and non-Burkitt's), and lymphoblastic malignancies.
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PMID:Expression of Tac antigen by non-Hodgkin's lymphomas. 282 94

Murine myeloma X63Ag8.653 cells were transfected with heavy and light-chain expression vectors for a chimeric antibody (Ab) to the human interleukin-2 receptor. A cell line producing low quantities of the chimeric Ab was obtained and was transfected with either the cytomegalovirus (CMV) immediate-early gene ie1 or Epstein-Barr virus (EBV) BMLF1 DNA, together with the hygromycin B resistance (HyR) encoding gene for selection to improve productivity. Two cell lines with a four to eightfold increase in productivity were obtained. They showed higher levels of heavy- and light-chain mRNA expression. CMV ie1 or EBV BMLF1 DNA was not detected and no integration pattern changes for the heavy- and light-chain DNA were seen. The long-term productivity of one of the cell lines showed hygromycin B (Hy) requirement. Transfection with the HyR DNA alone also resulted in cells with increased productivity. The expression vectors contained the immunoglobulin light-chain enhancer kappa B DNA sequences (kappa B site). Nuclear extracts from parent myeloma cells showed one kappa B-binding protein band on a polyacrylamide gel, but nuclear extracts from transfected cells showed two additional slower-migrating bands. Increased Ab production correlated with an increased ratio of the medium-mobility kappa B-binding protein band to the high-mobility band. The possibility that Hy used for selection activated kappa B-binding proteins and increased Ab expression is discussed.
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PMID:Transfection of murine myeloma cells to produce a chimeric antibody to the interleukin-2 receptor. 795 65

We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL-2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients with chronic lymphocytic leukemia (CLL) and evaluated them in relation to clinical and biological parameters of the disease, as well as serum immunoglobulin E (IgE). Compared to 31 normal individuals, 42 CLL patients had increased levels of sCD23 (98.4 +/- 127.7 versus 0.9 +/- 0.3 U/ml, p < 0.001), sIL-2R (6080 +/- 7030 versus 1420 +/- 640 pg/ml, p < 0.001), sTfR (12,100 +/- 11,250 versus 5000 +/- 1050 ng/ml, p < 0.001), and sCD8 (510 +/- 191 versus 234 +/- 89 U/ml, p < 0.001), but normal sCD4 levels. Mean sCD23 levels remained normal in patients with non-Hodgkin's lymphoma (other than small lymphocytic), Hodgkin's disease, hairy cell leukemia, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), multiple myeloma, or solid tumors. Advancing Rai clinical stage was associated with a progressive elevation of sCD23 (p < 0.001), while sCD8 (p < 0.05), sIL-2R (p < 0.001), and sTfR (p < 0.005) were highest in stage 2 patients. Discriminant analysis confirmed the value of soluble receptor determinations in the clinical evaluation of CLL patients. sCD23 correlated with sIL-2R (p < 0.001) and sTfR (p < 0.05) but not with sCD4 or sCD8, and displayed an inverse relationship with serum IgE (NS) and total gamma-globulin (p < 0.05). sIL-2R correlated with sCD23 (p < 0.001), sTfR (p < 0.001), sCD4 (p < 0.01), and sCD8 (p < 0.01). The lymphocyte count correlated with serum lactate dehydrogenase (LDH) (p < 0.05), sCD23 (p < 0.001) and sIL-2R (p < 0.01) but not sTfR, sCD8, or sCD4. Chemotherapy produced consistent reductions of sCD23 levels in two responding patients. We conclude that: (i) sCD23 is considerably elevated in CLL, correlates with the tumor mass and clinical stage, and could be helpful in monitoring these patients; and (ii) sIL-2R, sCD8, and sTfR levels are less specifically increased and could be influenced by other factors such as immune activation and erythropoiesis.
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PMID:Soluble CD23 and other receptors (CD4, CD8, CD25, CD71) in serum of patients with chronic lymphocytic leukemia. 825 2

Cytokines play a key-role in the immune response. The best known of them is interleukin-2 and its specific receptors. Monoclonal antibodies directed against the interleukin-2 receptor have initially enabled this receptor to be characterized; then they served to confirm the major role played by this cytokine in immune responses, where it proved effective in many animal models such as allograft reaction, delayed hypersensitivity reaction and some experimental auto-immune diseases. These results have been confirmed in man, particularly in kidney transplantation (but also in bone marrow transplantation), and they encourage to develop new bioreagents (chimeral antibodies, "humanized" antibodies, fusion proteins). Some of these reagents are now undergoing evaluation in renal transplantation. The principles of these bioreagents, issued from molecular biology, can be applied to other cytokines involved in the immunopathological mechanisms of certain diseases such as, for example, IL-6 and its role in the development of myeloma. Data from immune intervention directed against other cytokines are, for the moment, preliminary, but many potential targets (IL-1, IL-4, TNF alpha, INF gamma) are emerging.
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PMID:[Anti-cytokines and anti-cytokine receptors]. 834 28

Increased levels of soluble interleukin-2 receptor (sIL-2R) have been noted in the sera of patients with various diseases such as adult T cell leukemia, malignant lymphoma and autoimmune diseases. Using an enzyme-linked immunoabsorbent assay, we assessed sIL-2R levels in the sera of 16 patients with multiple myeloma (MM) and 27 normal subjects. There was a significant increase in the levels of sIL-2R in the patients with myeloma (963 +/- 523 U/ml) compared to normal subjects (213 +/- 80 U/ml). The levels of sIL-2R corresponded well with the clinical stage, M-protein, serum IL-6 and serum beta 2 microglobulin levels. Taking the evidence that the CD4/CD8 ratio decreased as the disease worsened into consideration, the increase in the serum sIL-2R levels of the patients with MM is considered to have some correlation with B and T cell activation through various cytokines including IL-6. Furthermore such evidence would support the role of sIL-2R as a disease monitor of MM.
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PMID:[Clinical significance of soluble interleukin-2 receptor in multiple myeloma]. 869 63

The serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble interleukin-2 receptor (sIL-2r), and interleukin-1alpha (IL-1alpha) were measured in 30 healthy subjects, 22 patients with monoclonal gammopathy of undetermined significance (MGUS), five patients with smoldering multiple myeloma (SMM), and 46 with multiple myeloma (MM). Serum levels of IL-6, TNF-alpha, and sIL-2r were significantly increased in patients with active MM when compared with normal controls. Furthermore, MM patients with advanced aggressive disease had significantly higher levels of IL-6, TNF-alpha, and sIL-2r than those with MM in plateau phase. In conclusion, our data support the involvement of IL-6, TNF-alpha, and sIL-2r in MM. This confirms recent in vitro studies suggesting that these cytokines may play a central role in the pathogenesis of MM. Our data also show that serum levels of TNF-alpha, sIL-2r, and, particularly, IL-6 could be useful in the clinical management of patients with MM.
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PMID:Cytokines (IL-6, TNF-alpha, IL-1alpha) and soluble interleukin-2 receptor as serum tumor markers in multiple myeloma. 890 3

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30+ target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30+ immune effectors and/or microenvironmental accessory cells.
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PMID:CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin. 905 27


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