Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biopsy specimens taken during exploratory laparotomy provided the material for a pathological study of 23 cases of nonsecreting immunoproliferative small intestinal disease (Mediterranean lymphomas without alpha-chain disease). The distinctive pathological feature of immunoproliferative small intestinal disease, i.e., a diffuse lymphoid infiltration, was present in the mucosa and submucosa of all or a major part of the small intestine. It was composed of a low- or intermediate-grade malignant lymphoid proliferation associated in 19 of 23 cases with benign-appearing follicular lymphoid structures. These follicular figures were surrounded and partially destroyed by the lymphoma cells. This association strongly resembles the newly described non-Hodgkin's lymphoma entities of perifollicular or parafollicular cell origin. Gross tumors of the small intestine were found in association with the diffuse lymphoid infiltration in 10 cases. They often constituted foci of lymphoma with a higher grade of malignancy. Mesenteric lymph node involvement was frequent and generally in direct ratio to the severity of intestinal involvement. A comprehensive study of the lesions observed in these cases led to the hypothesis that nonsecreting immunoproliferative small intestinal disease could result from the malignant change of perifollicular B cells; during an initial period the tumoral cells retain circulating and homing properties that explain their infiltrative and extensive method of spreading. The possible subsequent emergence of more aggressive subclones of noncirculating malignant cells could then explain the associated inconstant fungating tumor foci. Further studies using more sophisticated immunohistochemical techniques are necessary to establish the meaning of the hyperplastic lymphoid follicles, the possible etiologic role of benign nodular hyperplasia, the exact identification of the tumor cells, and the relationship of nonsecreting immunoproliferative small intestinal disease to closely related alpha-chain disease.
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PMID:Immunoproliferative small intestinal disease without alpha-chain disease: a pathological study. 291 38

We investigated the expression of interleukin-2 receptors (IL-2R) in 60 adult patients with mature lymphoid neoplasms by flow cytometric analysis, using two monoclonal antibodies, anti-Tac for IL-2R alpha-chain (IL-2R alpha) and Mik-beta 1 for IL-2R beta-chain (IL-2R beta). Among B-cell malignancies, IL-2R alpha was found in 13/25 (52%) cases of chronic lymphocytic leukemia (CLL) and its variants, 3/14 (21%) of a heterogeneous group of non-Hodgkin's lymphoma (NHL) and none of the plasma cell diseases. IL-2R beta was not observed in any of B-cell neoplasms. IL-2R alpha was more frequently expressed in CD11b(+) B-cell neoplasms than in CD11b(-) (P < 0.05). In T-cell disorders, all three cases of adult T-cell leukemia/lymphoma expressed IL-2R alpha but not IL-2R beta. IL-2R beta was detected in 3/8 cases of CLL and 2/3 of NHL and none of these cases expressed IL-2R alpha. CD8(+) malignant T-cells commonly displayed IL-2R beta. These data indicate that the IL-2R alpha and IL-2R beta in mature lymphoid neoplasms was expressed independently each other and was associated with the particular phenotypical characteristics of neoplastic cells, respectively.
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PMID:Differential expression of interleukin-2 receptors (alpha and beta chain) in mature lymphoid neoplasms. 751 48

Prolymphocytic leukemia (PLL) is closely related to chronic lymphocytic leukemia (CLL), but present with distinctive clinical/laboratory features and associated with much worse prognosis. In this study, we generated three new IgG1-kappa monoclonal antibodies (MoAbs), termed SN8, SN8a and SN8b, by use of an unconventional approach, ie, by using an isolated B PLL antigen preparation to immunize mice. These MoAbs, particularly SN8, showed a highly selective reactivity to B PLL and B non-Hodgkin's lymphoma (NHL) among various human leukemia-lymphoma specimens tested; eg, SN8 was capable of effectively distinguishing B PLL from B CLL as well as from hairy cell leukemia (HCL) cell specimens. The cell surface antigen defined by the three MoAbs was determined to be a covalently linked heterodimeric glycoprotein complex (gp49/40) consisting of a 49,000 dalton (alpha-chain) and a 40,000-dalton component (beta-chain). Epitope comparison showed that the epitope defined by SN8 (SN8 epitope) is in close proximity to SN8a epitope but in a distant position from SN8b epitope. Western blot analysis showed that both SN8 and SN8a epitopes are on the beta-chain, but SN8b epitope was not detected on either the alpha- or the beta-chain of the reduced antigen in the same analysis. Binding of either SN8 or SN8b to the cell surface gp49/40 did not cause significant downregulation of the antigen expression whereas binding of SN8a to the antigen caused small (approximately 20%) decrease in the antigen expression. Among the various normal peripheral blood cells, only a subpopulation (6.0% to 24.2% among different specimens derived from different donors) of B cells reacted with the SN8 series MoAbs; these MoAbs showed no significant reactivity against T cells, granulocytes, monocytes, erythrocytes, and platelets. Minimal or no significant reactivity (0 to 2.6% among different specimens) was detected against normal bone marrow cells. Ricin A-chain conjugates of the three MoAbs are all strongly effective for specific killing of SN8 antigen-expressing leukemia cells in the absence of any potentiators; furthermore, the addition of 10 mmol/L NH4Cl, a potentiator, enhanced strongly the cytotoxic activities of the SN8, SN8a, and SN8b conjugates. Thus, each of the three MoAbs was effectively internalized after binding to the cell surface antigen.
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PMID:Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively internalized after binding to the cell surface antigen. 841 5

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

Lymphohematopoietic malignancies are common spontaneous diseases of dogs whose clinical presentation and biologic behavior closely resemble their human counterparts. The goal of this study was to define the potential to use canine lymphoma and leukemia as suitable models to refine therapeutic approaches targeting the interleukin-2 receptor (IL-2R). The authors evaluated the patterns of IL-2R expression in 13 dogs with multicentric non-Hodgkin's lymphoma (NHL) and in six dogs with leukemia (acute lymphocytic leukemia, n = 3; chronic lymphocytic leukemia in blast crisis, n = 1; acute monoblastic leukemia, n = 2). The authors first cloned and sequenced the complete coding domains of the wild-type canine IL-2R alpha-chain gene. They next used qualitative reverse transcription polymerase chain reaction (RT-PCR) analysis to examine IL-2R alpha, beta, and gamma(c) subunit expression in the tumors. Messenger RNA (mRNA) for the interleukin-2 receptor alpha, beta, and gammac subunits that comprise the high-affinity receptor was present in samples from all dogs with NHL. Expression of functional surface IL-2R also was observed flow cytometrically in NHL cells from all four dogs tested. Leukemic cells from one dog with B cell acute lymphocytic leukemia and two dogs with acute monoblastic leukemia expressed mRNA for all three subunits, whereas cells from another dog with B cell leukemia and both dogs with T cell leukemia expressed only mRNA for the beta and gammac subunits that comprise the intermediate-affinity receptor. These results indicate that the IL-2R is commonly expressed in canine lymphohematopoietic malignancies, and support the suitability of this large-animal model to evaluate targeted IL-2R cancer therapy using approaches of interest in the treatment of humans with hemolymphatic cancers.
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PMID:Potential to target dysregulated interleukin-2 receptor expression in canine lymphoid and hematopoietic malignancies as a model for human cancer. 1192 9