Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent report revealed that a large population of Hodgkin's lymphoma-infiltrating lymphocytes (HLILs) consisted of regulatory T cells. In this study, we cocultured CD4+ naive T cells with KM-H2, which was established as a Hodgkin's Reed-Sternberg cell line, to clarify their ability to induce CD25+ Forkhead box P3+ (Foxp3+) T cells. The characteristic analyses of T cells cocultured with KM-H2 revealed the presence of CD4+CD25+ T cells. They expressed CTLA-4, glucocorticoid-induced TNFR family-related gene, and Foxp3 and could produce large amounts of IL-10. Conversely, KM-H2 also generated CD4+ CTLs, which expressed Granzyme B and T cell intracellular antigen-1 in addition to Foxp3+ T cells. They exhibit a strong cytotoxic effect against the parental KM-H2. In conclusion, KM-H2 promotes a bidirectional differentiation of CD4+ naive T cells toward Foxp3+ T cells and CD4+ CTLs. In addition to KM-H2, several cell lines that exhibit the APC function were able to generate Foxp3+ T cells and CD4+ CTLs. Conversely, the APC nonfunctioning cell lines examined did not induce both types of cells. Our findings suggest that the APC function of tumor cells is essential for the differentiation of CD4+ naive T cells into CD25+Foxp3+ T cells and CD4+ CTLs and at least partly explains the predominance of CD25+Foxp3+ T cells in HLILs and their contribution to a better prognosis. Therefore, in APC-functioning tumors, including classical Hodgkin lymphomas, which generate Foxp3+ T cells and CD4+ CTLs, these T cell repertories play a beneficial role synergistically in disease stability.
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PMID:Hodgkin's reed-sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells. 1754 18

Recent studies in mice have shown a role for the canonical WNT pathway in lymphocyte development. Because cancers often arise as a result of aberrant activation of signaling cascades that normally promote the self-renewal and expansion of their progenitor cells, we hypothesized that activation of the WNT pathway might contribute to the pathogenesis of lymphoproliferative disease. Therefore, we screened a large panel (n = 162) of non-Hodgkin lymphomas (NHL), including all major WHO categories, for nuclear expression of beta-catenin, a hallmark of "active" WNT signaling. In 16 lymphomas, mostly of T-lineage origin, nuclear localization of beta-catenin was detected. Interestingly, some of these tumors contained established gain-of-function mutations in the gene encoding beta-catenin (CTNNB1); however, in the majority, mutations in either CTNNB1 or APC were not detected. Functional analysis of WNT signaling in precursor T-lymphoblastic lymphomas/leukemias, the NHL subset in which beta-catenin accumulation was most prevalent (33% positive), revealed a constitutively activated, but still responsive, WNT pathway, which controlled T-cell factor-mediated gene transcription and cell growth. Our data indicate that activation of the WNT pathway, either by CTNNB1 mutation or autocrine stimulation, plays a role in the pathogenesis of a subset of NHLs, in particular, those of T-cell origin.
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PMID:Illegitimate WNT pathway activation by beta-catenin mutation or autocrine stimulation in T-cell malignancies. 1875 11

The diagnosis of classical Hodgkin lymphoma (CHL) has been made in tissue sections as attempts to identify neoplastic Hodgkin and Reed Sternberg (HRS) cells in lymph nodes by flow cytometry (FC) have been unsuccessful. However, we have recently demonstrated that HRS cells can be identified by FC, often present as T-cell-HRS-cell rosettes. In this study, we examined the usefulness of a novel 9-color (CD95-Pacific blue/CD64-fluorescein isothiocyanate/CD30-phycoerythrin [PE]/CD45-PE-Texas red/CD40-PE cyanine [Cy]5.5/CD20-PECy7/CD15-allophycocyanin [APC]/CD71-APC-AlexaFluor A700/CD5-APC-Cy7), single tube FC assay to diagnose CHL in lymph nodes. We used the FC assay to determine diagnostic sensitivity and specificity in 279 blindly identified and 141 selected (for specimen type or cytopreparation morphologic features suggesting CHL) tissues. Of the 53 morphologically defined CHL cases identified (10 in the unselected group; 43 in the selected group), the FC assay diagnostic sensitivity and specificity were 88.7% and 100%, respectively. With the current availability of 8 (or more) color clinical flow cytometers, this assay can now be applied to routinely immunophenotype and confirm a diagnosis of CHL or as an adjunct to immunohistochemical analysis.
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PMID:Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity. 1922 36

We analyzed 66 cases of immune-mediated thrombophilia in patients with lymphoma reported in the literature. Sixty-one cases had a lupus anticoagulant, three an antibody to protein S, one to protein C, and one to ADAMTS 13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Lupus anticoagulants occurred in all histological subtypes of non-Hodgkin lymphoma, except mantle cell lymphoma, MALT (mucosa-associated lymphoid tissue) lymphoma, and angioimmunoblastic T-cell lymphoma, and rarely in Hodgkin lymphoma. The largest number of cases was described in splenic marginal zone and lymphoplasmacytic lymphoma. Lupus anticoagulants were highly associated with immunoglobulin M (IgM) paraproteinemia, autoimmune hemolytic anemia, and immune thrombocytopenia. About half of the patients had thrombotic events (antiphospholipid antibody syndrome). Venous thromboembolism was more than twice as common as arterial thrombosis; 6.5% had a catastrophic antiphospholipid antibody syndrome. The lupus anticoagulant could be eliminated by lymphoma treatment (chemoimmunotherapy or splenectomy) in more than one-third of patients. It is suggested that a search for lupus anticoagulant should be done in all patients with lymphoma, because a diagnosis of lupus anticoagulant may influence the management of lymphomas in some patients.
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PMID:Acquired immune-mediated thrombophilia in lymphoproliferative disorders. 2176 5


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