Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angioimmunoblastic T-cell lymphoma (AILT) is a malignant disease of peripheral T-cell origin that is characterized by a prominent proliferation of high endothelial venules in the lymph node. To investigate angiogenic mechanisms in AILT we measured the angiogenic mediator gene expression levels in the lymph nodes of 54 non-Hodgkin lymphoma patients, by immunostaining and quantitative reverse transcription polymerase chain reaction. Angiogenic mediators angiopoietin (Ang) 1 (ANGPT1), Ang2 (ANGPT2) and their receptor, Tie2 (TEK), vascular endothelial growth factor (VEGF; VEGFA) and its receptor, VEGFR2 (KDR), and hepatocyte growth factor (HGF) and its receptor, c-Met (MET) were all more highly expressed in AILT lymph nodes (16 cases) than in B-cell lymphomas (24 cases). Moreover, significantly higher Ang1 and Tie2 expression was detected in AILT cases with CD10-positive neoplastic T-cells by comparison with unspecified peripheral T-cell lymphoma (14 cases). Immunostaining confirmed the expression of Ang1 and VEGF by both neoplastic T-cells and follicular dendritic cells. These results suggest that the angiopoietin system may play an important role in the development of high vascularity in AILT lymph nodes. Consequently, as neoplastic T-cells and follicular dendritic cells are both increased in AILT and may represent an important source of angiogenic mediators, targeting these cells with anti-angiogenic strategies might represent a novel therapy for AILT.
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PMID:Angiogenic mediators of the angiopoietin system are highly expressed by CD10-positive lymphoma cells in angioimmunoblastic T-cell lymphoma. 1912 Mar 65

Angioimmunoblastic T-cell lymphoma is an aggressive peripheral T-cell lymphoma whose natural history is not fully understood. Up to 17% of cases can present histologically with hyperplastic germinal centres (pattern I). The accurate recognition of Angioimmunoblastic T-cell lymphoma with pattern I remains a challenge and therefore the aim of this study is to phenotypically and morphologically characterize this variant with the use of the follicular helper T-cell (T(FH)) markers PD1, CXCL-13 and ICOS. Out of the 88 Angioimmunoblastic T-cell lymphoma cases reviewed, 10 showed hyperplastic follicles. Molecular probe methods for the detection of T-cell and B-cell clonality, as well as in-situ hybridization probes for EBV RNA expression, were carried out to leave no question as to the establishment of the diagnosis in each case. Of the 10 cases, all (100%) showed strong positive PD1 staining in perifollicular areas and in neoplastic cells surrounding small veins. CXCL13 and ICOS showed a similar staining pattern. By contrast, CD10 was found to only weakly label the neoplastic T cells, with only 5-10% of the target cell population staining for this marker. EBV was found in 9/10 cases. Clinically, 8/9 cases presented with stage IIIB/IVB and in 2/10 cases consecutive biopsies showed 'progression' from pattern I to classical Angioimmunoblastic T-cell lymphoma. In conclusion we have shown that the T(FH) cells markers PD1, CXCL13 and ICOS are useful adjuncts in the diagnosis of Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres. PD1 also highlighted the presence of neoplastic cells in the outer zone of lymphoid follicles, suggesting that Angioimmunoblastic T-cell lymphoma (pattern I) may originate from T(FH) cells in this region, in accordance with previous immunological studies. As the majority of cases in our series presented clinically with advanced stage disease, progression from pattern I to classical Angioimmunoblastic T-cell lymphoma may represent histological evolution rather than clinical progression.
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PMID:Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres: a neoplasia with origin in the outer zone of the germinal centre? Clinicopathological and immunohistochemical study of 10 cases with follicular T-cell markers. 1932 36

We retrospectively reviewed the clinical and laboratory data and bone marrow (BM) histomorphologic features in 33 angioimmunoblastic T-cell lymphoma (AITL) cases. Paraffin-embedded BM core biopsy specimens were reacted immunohistochemically with antibodies to pan-T-cell markers, CD20, CD10, CD21, and bcl-6. The frequency of BM involvement was 70% (23/33). The following features were more significant in patients with than without BM involvement: fever, hepatosplenomegaly, pleural effusion, elevated lactate dehydrogenase level, hypoalbuminemia, hyponatremia, hypocalcemia, anemia, circulating atypical cells, hypercellular marrow, and plasmacytosis in the BM. Morphologic features included nodular or interstitial infiltration in a paratrabecular distribution, periodic acid-Schiff-positive intercellular materials, mixed infiltrates of T and B cells, presence of clear cells, and blood vessel proliferation. Immunohistochemical assays revealed that CD5, bcl-6, and CD10 were useful markers of BM infiltration. Seven cases with BM involvement were interpreted as negative for lymphoma initially, mainly owing to insufficient information in nodal biopsy specimens. Several clinical and laboratory features indicate BM involvement of AITL at diagnosis. Laboratory physicians should be more familiar with BM histomorphologic and immunophenotypic characteristics suggesting AITL infiltration to make accurate diagnoses even without prior nodal biopsies.
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PMID:Distinct features of angioimmunoblastic T-cell lymphoma with bone marrow involvement. 1936 22

Patients affected by autoimmune diseases (rheumatoid arthritis (RA), psoriasis, and dermatomyositis) treated with methotrexate (MTX) develop lymphoproliferative disorders (LPDs). These cases have been reported to be diffuse large B-cell lymphoma, Hodgkin lymphoma, or polymorphous post-transplant LPDs. However, angioimmunoblastic T-cell lymphoma (AITL) is extremely rare in the medical literature. In this report, we describe three cases of RA patients who developed MTX-associated LPDs resembling AITL. They developed systemic lymph node swelling after initiation of MTX. The affected lymph nodes showed the histological finding of AITL: polymorphous infiltrates, mainly T-cells and arborizing high endothelial venules. Two cases showed a predominance of CD4-positive cells in proliferative T-cells, whereas the third case showed CD8-positive cells. CD10 was negative in all cases. RNA in situ hybridization of Epstein-Barr virus (EBV) demonstrated EBV-positive B-cells to be scattered in two cases, but not in one case. The lymphoadenopathy spontaneously regressed with cessation of MTX in all three cases, but one case recurred. These are interesting cases of MTX-associated LPDs mimicking AITL, and cessation of MTX is the only cure for patients with MTX-associated LPDs resembling AITL.
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PMID:Methotrexate-associated lymphoproliferative disorders mimicking angioimmunoblastic T-cell lymphoma. 1962 40

T cells coexpressing CD3 and CD10 are a characteristic feature of angioimmunoblastic T-cell lymphoma (AITL) [1]. However, they are not unique to AITL, as these cells are also present in B cell lymphoma and reactive lymphoid hyperplasia [2]. To determine the significance of CD3+ CD10+ T cells, we used flow cytometry with cell sorting and molecular biology techniques for T cell gene rearrangement to study T cells from patients with AITL, B cell lymphoma, and reactive lymph node hyperplasia. We found that CD3+ CD10+ T cells in B cell lymphoma and reactive lymphoid hyperplasia were polyclonal. In early stage of AITL, they were oligoclonal, and became monoclonal as AITL progressed. These findings illustrate the differences between early and late lymphoma and could be important for the diagnosis of AITL.
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PMID:The clonality of CD3+ CD10+ T cells in angioimmunoblastic T cell lymphoma, B cell lymphoma, and reactive lymphoid hyperplasia. 1965 Jan 43

Angioimmunoblastic T-cell lymphoma is known to frequently involve bone marrow. However, the histologic and immunophenotypic features of angioimmunoblastic T-cell lymphoma at this site are poorly defined. We assessed 27 bone marrow specimens involved by angioimmunoblastic T-cell lymphoma from 20 patients. Histologically, bone marrow involvement was predominantly multifocal (74%) and exhibited a nodular pattern (78%), often associated with other patterns. Using immunohistochemistry, programed death-1 and CD10 were expressed by atypical lymphocytes in 17 (85%) of 20 and 5 (18.5%) of 27 specimens, respectively. CXCL13 was not expressed by atypical lymphocytes in all cases but did stain stromal cells consistent with follicular dendritic cells in 1 case. BCL-6 as a single antibody was difficult to interpret because many normal bone marrow cells are dimly positive, but BCL-6/CD3 dual staining highlighted BCL-6+ T-cells in all cases assessed. Antibodies specific for CD21 and CD35 did not highlight follicular dendritic cells in any biopsy specimens. Flow cytometry immunophenotyping revealed a CD3+CD10+ T-cell population in 2 (25%) of 8 cases assessed. We conclude that the recognition and classification of angioimmunoblastic T-cell lymphoma in bone marrow are made difficult by the uncommon expression of CD10 (25%), rarity of follicular dendritic cells, and lack of CXCL13 expression at this site. This is most likely attributable to the very different microenvironment of the bone marrow relative to lymph nodes and, in particular, the absence of follicles in bone marrow. By contrast, programed death-1 immunohistochemical staining and double labeling using antibodies specific for BCL-6 and CD3 were helpful in appreciating the follicular T-helper cell immunophenotype of angioimmunoblastic T-cell lymphoma.
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PMID:Angioimmunoblastic T-cell lymphoma in bone marrow: a morphologic and immunophenotypic study. 1974 May 19

Angioimmunoblastic lymphoma (AITL) is a nodal peripheral T-cell lymphoma characterized by a proliferation of arborizing vessels and hyperplastic follicular dendritic cells as well as a polymorphous lymphoid infiltrate including neoplastic cells with clear cytoplasm. Adult T-cell leukemia/lymphoma (ATLL) is caused by the retrovirus human T-cell leukemia virus type I (HTLV-I), and the neoplastic cells are usually large and pleomorphic. Recently, a rare morphologic variant of ATLL with AITL-like features has been reported. Here, we presented a case of peripheral T-cell lymphoma with morphological features of AITL in Taiwan, a country non-endemic for HTLV, and the patient was seropositive for anti-HTLV antibody, which raised the possibility of ATLL with AITL-like features. Immunohistochemically, there were hyperplastic follicular dendritic meshworks by CD21 immunostaining, and the neoplastic cells expressed CD10, programmed death-1, and CXCL13. Furthermore, Southern blot analysis using DNA extracted from the nodal tissue was negative for HTLV-I proviral integration. Our investigations indicated that in an HTLV-I non-endemic area, a peripheral T-cell lymphoma with typical morphologic and immunophenotypic features of AITL could be confidently diagnosed as AITL even if the patient was seropositive for anti-HTLV antibody.
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PMID:Differential diagnosis of angioimmunoblastic T-cell lymphoma with seropositivity for anti-HTLV antibody from adult T-cell leukemia/lymphoma. 2019 59

Angioimmunoblastic T-cell lymphoma is immunologically defined by the expression of CD10 and the follicular helper T cell (T(FH)) markers such as CXCL13, programmed death-1 (PD-1) and inducible T-cell costimulator (ICOS). This T(FH) profile has been mainly reported by immunohistochemistry. Here, using multiparametric flow cytometry, the relevance of ICOS and PD-1 to angioimmunoblastic T-cell lymphoma diagnosis was evaluated in lymph node (n=15) as well as in peripheral blood (n=13) among a series of 28 angioimmunoblastic T-cell lymphoma cases, in addition to the CD10 expression (available in 26 lymph node and 15 peripheral blood specimens). In this series, CD10 expression was present in 23/26 (88%) lymph node and in 12/15 (80%) peripheral blood cases and ICOS in 13/15 (87%) lymph node and in 6/13 (47%) peripheral blood cases, whereas neither significant CD10 nor ICOS T cells were identified in the control group (lymph nodes with reactive hyperplasia=10, peripheral blood of healthy donors=15). PD-1 expression was less informative as observed in both angioimmunoblastic T-cell lymphoma and control cases. The multiparametric approach allowed us to confirm the frequent blood dissemination in angioimmunoblastic T-cell lymphoma and to show that circulating neoplastic T cells correspond more often to a CD10-positive subset than to an ICOS-positive subset. Consequently, if ICOS constitutes an additional feature for the diagnosis of angioimmunoblastic T-cell lymphoma, it appears less sensitive than CD10 expression for the detection of circulating neoplastic T cells.
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PMID:CD10 and ICOS expression by multiparametric flow cytometry in angioimmunoblastic T-cell lymphoma. 2149 31

The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.
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PMID:BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma. 2232 90

We examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma, follicular variant (f-PTCL), and compared these findings with angioimmunoblastic T-cell lymphoma (AITL) to determine whether they were identical to the spectrum of changes seen in AITL and how each of the findings in f-PTCL were related to the characteristics of AITL. Almost all f-PTCL cases showed pathologic characteristics of AITL and immunohistochemical positivities in lymphoma cells for CD4, CD10, Bcl-6, PD-1, and CXCL13. Except for pathologic characteristics, clinicopathologic findings in f-PTCL had few significant differences from AITL. The positive rate for Bcl-6 expression in neoplastic cells was significantly associated with the frequency of polymorphic infiltrates, vascular proliferation, B-immunoblasts, clear cells, Epstein-Barr virus-positive lymphocytes, hepatosplenomegaly, and skin rash. Our study confirmed the continuity between f-PTCL and AITL. Moreover, Bcl-6 expression in f-PTCL was statistically associated with the characteristics of AITL.
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PMID:Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioimmunoblastic T-cell lymphoma: Bcl-6 expression might affect progression between these disorders. 2258 46


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