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)

Mediastinal large B cell lymphomas are uncommon neoplasms that are thought to originate from thymic B cells. An unusual feature of these neoplasms is that they often lack surface immunoglobulin (Ig), a molecule ubiquitously expressed by most mature B cells. In the present study we have analyzed 12 cases of mediastinal large B cell lymphoma for the expression of the mb-1/CD79a polypeptide. This is a component, together with B29/CD79b, of a heterodimer that is associated with surface Ig on normal B cells. Our aim was to see whether loss of Ig in this type of lymphoma is associated with loss of the accompanying CD79a molecule. We have also evaluated 128 B cell lymphomas of other categories to see whether any of them show discordance between mb-1 and Ig expression and analyzed 30 T cell lymphomas as Ig-negative controls. We found that 5 of the 7 mediastinal large B cell lymphomas with interpretable staining results for both mb-1 and Ig, lack Ig but expressed CD79a (mb-1). This phenotype was very rare in other categories of B cell lymphoma, being found among 110 cases in only 5 cases that were all follicular lymphoma. The remaining 105 B cell lymphomas displayed mb-1+/Ig+ phenotype. All 30 T cell lymphomas were mb-1 negative. We conclude that discordant mb-1/Ig expression occurs commonly in mediastinal large B cell lymphomas. In addition, the finding that 11 of 12 of these neoplasms express a phenotype (CD10-, CD19+, CD20+, CD21-, CD22+, CD23-/+) that is very similar to that described for thymic medullary B cells reinforces the idea that most mediastinal large B cell lymphomas are of thymic B cell origin. The correlation between mb-1 and Ig staining patterns in B cell lymphomas of other categories reveals that in the majority (90%), expression of the antigen receptor complex parallels that of mature B cells. These data therefore confirm that the expression of the mb-1 protein provides independent strong evidence for the B lineage of lymphomas and may be used for their routine phenotypic characterization.
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PMID:Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas. 788 54

A large number of continuous human leukemia cell lines have been established over the last three decades. Clearly, leukemia cell lines have become important research tools. Here, we have summarized the immunological, molecular and standard cytogenetic features of a panel of well characterized B cell precursor (BCP)-leukemia cell lines which were derived from patients with acute lymphoblastic/undifferentiated leukemia (ALL/AUL) or chronic myeloid leukemia (CML) in blast crisis. Following the recently proposed immunological EGIL classification, we assigned our panel of 27 BCP-cell lines to one of the following categories: B-I pro-B cell line; B-II common-B cell line; and B-III pre-B cell line. All cell lines express general B-lineage associated surface markers (HLA-DR, CD22, CD79a) being negative for surface immunoglobulin (Ig); the differences between the subgroups reside in expression of CD10 and cytoplasmic Ig. Several BCP-cell lines show the myelomonocytic cell-associated markers CD13 and/or CD33. These immunologically 'biphenotypic' BCP-cell lines are generally TdT+ CD10+ CD13+ CD19+ CD22+ CD34+ and carry the Philadelphia (Ph) translocation. The BCP-cell lines display surface receptors for interferon-gamma (CD119), interleukin-7 (CD127) and FLT-3 ligand (CD135). All BCP-cell lines examined have complex numerical and structural chromosomal alterations including translocations commonly seen in BCP-ALL such as t(4;11), t(9;22), t(11;19), t(12;21), and t(17;19) involving the fusion genes MLL-AF4, BCR-ABL, ENL-MLL, TEL/ETV6-AML1 and E2A-HLF, respectively. Besides the expected rearrangement of the Ig heavy chain receptor gene, several cell lines also have rearrangements of the T cell receptor genes beta, gamma or delta. While some BCP-cell lines express (aberrantly) myeloperoxidase at the mRNA level, most lines are negative in the immunological or cytochemical staining. Several large series documented the difficulty in establishing such BCP cell lines with success rates in the range of 10-20% (on average 15%). Still, since the establishment of the first bonafide BCP-cell line in 1974 (cell line REH), some 150 cell lines have been established of which, however, only a small percentage have been sufficiently well characterized and described. A higher success rate for immortalizing any given leukemia cell might depend on a closer emulation of the physiological in vivo microenvironment. The possibility to grow in vitro leukemia cells at will would represent ideal experimental systems permitting basic research and patient-specific investigations. In summary, the use of well-characterized BCP-cell lines provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic B-lymphocytes.
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PMID:Establishment and characterization of human B cell precursor-leukemia cell lines. 968 Jan 6

Terminal deoxynucleotidyl transferase (TdT)-positive cells in human bone marrow (BM) are a phenotypically inhomogeneous population of precursor cells. In their majority, these TdT+ cells are unambiguously committed to the B lineage, as evidenced by CD19 expression. However, TdT+ precursors that lack CD19 also exist and these may encompass a differentiation potential for the B as well as for other lineages. Because recent data suggested that CD19 expression is not the earliest differentiation event in B-cell ontogeny, we sought to reevaluate TdT+ lymphoid precursors in pediatric BM to define the phenotypic denominator of B-lineage affiliation upstream of CD19. Using four-color flow cytometry, we focused on the assessment of the CD79a antigen, which is highly B-cell specific and which may also be expressed very early in B-cell ontogeny. We found that a majority of TdT+ cells coexpressed CD19 and CD79a in addition to CD10 and CD34, whereas, in all investigated samples, some TdT+ precursors lacked CD19 but expressed CD79a, which suggestively indicates also their B-lineage affiliation. In contrast to the CD19(+) precursors, which were usually CD10(hi) and CD79b+, these CD19(-)CD79a+ putative B-cell precursors preferentially expressed CD10 at low levels and were CD79b+ in only 41%. About 17% of these TdT+CD19(-)CD79a+ precursors also coexpressed CD33 and CD7, but not myeloperoxidase, CD14, or cytoplasmic CD3, which is discussed in the light of cellular activation rather than lineage promiscuity. Our data confirm that the earliest differentiation stages of B cells can be dissected upon expression of the lineage antigens CD79a and CD19 and imply that CD79a is earlier expressed than CD19. This raises the chance to follow the sequential events heralding B-cell commitment in the most immature precursors by correlating phenotypic and genetic differentiation markers.
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PMID:Four-color flow cytometric investigation of terminal deoxynucleotidyl transferase-positive lymphoid precursors in pediatric bone marrow: CD79a expression precedes CD19 in early B-cell ontogeny. 978 56

We report 2 cases of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type presenting as primary lesions in the intracranial dura. Both patients are female, and, prior to biopsy were felt to have subdural hematoma and meningioma based on preoperative MRI scans. Histologically, both cases showed a diffuse proliferation of small centrocyte-like cells or monocytoid B cells admixed with a moderate number of large transformed cells. Reactive germinal center formation was present, as was plasmacytoid differentiation in one case. These histologic features are identical to those associated with low-grade MALT lymphomas arising at other more typical sites. Clinically, both patients were found to have stage IE disease at diagnosis without evidence of lymphoma outside of the central nervous system. Immunophenotypically, the lymphomas expressed B-cell-associated antigens CD20 and CD79a without coexpression of CD5, CD10, or CD23, and 1 of the 2 cases tested showed monoclonal rearrangement of the immunoglobulin heavy chain gene without rearrangement of bcl-1 or bcl-2. MALT lymphomas have recently been described in the dura and are postulated to arise in association with meningoepithelial cells. It is important that this entity be recognized and distinguished from other small B-cell non-Hodgkin's lymphomas such as mantle cell lymphoma, small lymphocytic lymphoma, or follicular small cleaved cell lymphomas, since localized low grade MALT lymphomas are usually clinically indolent proliferations which may require only minimally aggressive therapy.
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PMID:Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in dura. 983 58

The immunoperoxidase technique was used with antibodies against B-cell-associated antigens, including CD20, CD79a, CD10, CD23, CD43, cyclin D1, bcl-2, and kappa and lambda immunoglobulin light chains on formalin-fixed and B5-fixed tissue sections of follicular, small lymphocytic, mantle cell, and marginal zone lymphomas. Results obtained with paraffin section immunohistochemistry for CD20, CD10, CD23, and kappa and lambda light chains were compared with results obtained with flow cytometry or frozen section immunohistochemistry. Cells in all of the lymphoma types were positive for CD20 and CD79a. The antigenic profiles of the B-cell lymphomas demonstrated in paraffin sections were lymphoma type distinctive. Intrafollicular lymphocytes in follicular lymphomas were positive for CD10 and bcl-2. Small lymphocytic lymphomas expressed CD43 and CD23 and were negative for CD10 and cyclin D1. Mantle cell lymphomas characteristically expressed CD43 and cyclin D1 and were negative for CD23 and CD10. Marginal zone lymphomas were negative for CD23, CD10, and cyclin D1. All of the antibodies performed better in B5-fixed tissues, but formalin-fixed tissue immunophenotypes were always similar to those obtained on the B5-fixed tissue. These results were possible using well-fixed tissue, various antigen retrieval strategies, paraffin section reactive primary antibodies, and sensitive detection systems. Paraffin section immunohistochemistry on sections of routinely fixed tissue can be used similarly to flow cytometry and frozen section immunohistochemistry when classifying the lymphomas of small B lymphocytes.
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PMID:Demonstration of distinct antigenic profiles of small B-cell lymphomas by paraffin section immunohistochemistry. 1047 36

Lymphoblastic leukemia/lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes of B- or T-cell phenotype. Involvement of the skin is relatively uncommon. We examined retrospectively the clinicopathologic, immunophenotypic, and molecular genetic features of six patients with cutaneous involvement of LBL (B-LBL=5; T-LBL=1). Patients presented clinically with solitary, large tumors located on the head (3 cases) or the back (1 case), or with generalized tumors (2 cases). Ulceration was uncommon. In two patients the onset of skin lesions was concomitant to the diagnosis of lymphoblastic leukemia. Histopathologic examination showed in all cases a dense, diffuse, monomorphous infiltrate located in the entire dennis and subcutaneous fat. A typical "starry sky" pattern was observed in the majority of the lesions. In some areas neoplastic cells were aligned in a "mosaic-like" fashion. Cytomorphologically, medium sized lymphoid cells with round or convoluted nuclei, inconspicuous nucleoli and scant cytoplasm predominated. There were no significant differences in the histopathologic features of skin lesions in T- and B-LBL. In B-LBL, CD79a was more useful than CD20 in determining the phenotype of neoplastic cells (4/5 cases positive for CD79a as compared to 2/5 cases positive for CD20). TdT, CD10 and CD43 were positive in 4 cases, CD34 in 2. The case of T-LBL revealed positivity for CD1a, CD3, CD43 and TdT, and negativity for CD34 and for B-cell markers. All neoplasms were positive for CD99 and bcl-2, and showed a high proliferation rate. Molecular genetic analysis of J(H) and T-cell receptor (TCR) genes performed using a polymerase chain reaction technique revealed a monoclonal rearrangement of J(H) genes in all five B-LBLs. One of these cases showed also a concomitant TCR-gamma gene rearrangement. A monoclonal rearrangement of the TCR-gamma gene was detected in the case of T-LBL. Our study shows that skin lesions of LBL present characteristic clinicopathologic and molecular features allowing the differentiation from other cutaneous lymphomas, even in cases without clinical history of previous precursor lymphoblastic leukemia/lymphoma.
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PMID:Cutaneous involvement in lymphoblastic lymphoma. 1055 9

Precursor B lymphoblastic lymphoma is an aggressive but potentially curable disease. This lymphoma most often manifests in the skin and lymph nodes and, less commonly, as lytic bone lesions. In the bone, this lymphoma must be differentiated from small round blue cell tumors, diffuse large B-cell lymphoma, and acute myelogenous leukemia. We describe the morphologic and immunophenotypic features in 4 patients, 2 children, 1 teenager, and 1 adult, who initially presented with bone pain and osteolytic lesions but without peripheral blood or iliac bone marrow involvement. Positive immunohistochemical staining of the neoplastic cells was observed for anti-CD10 (3/4), CD20 (3/4), CD34 (1/4), CD43 (4/4), CD45/CD45RB (2/4), CD79a (4/4), CD99 (MIC2) (2/4), and terminal deoxynucleotidyl transferase (4/4). CD3 was absent in all cases. Immunophenotyping these neoplasms is essential to establish the correct diagnosis of precursor B lymphoblastic lymphoma, and a panel of antibodies is required because of the immunophenotypic heterogeneity.
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PMID:Precursor B lymphoblastic lymphoma presenting as lytic bone lesions. 1058 7

The aim of this study was to establish how effective is the use of immunohistochemistry on formalin-fixed bone marrow in diagnosing low-grade B-cell neoplasms. We investigated a series of 41 consecutive patients with bone marrow involvement for whom no other diagnostic tissues were available. The sections were stained with the following antibodies: CD3, CD20, CD79a, CD5, CD10, CD23, anti-cyclin D1 and kappa and lambda light chains. Antigen retrieval was performed using either a microwave oven or a pressure cooker. Labelling was performed with an avidin-biotin-peroxidase labelling system. A final diagnosis was reached in 37 out of 41 cases (90%): B-chronic lymphocytic leukaemia (15 cases), follicular lymphoma (10 cases), mantle-cell lymphoma (eight cases) and lymphoplasmacytoid lymphoma/immunocytoma (four cases). In the remaining four cases, a generic diagnosis of low-grade B-cell neoplasm was made. The immunophenotyping of formalin-fixed marrow is a useful technique for diagnosing most of the low-grade B-cell neoplasms.
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PMID:The diagnosis of low-grade peripheral B-cell neoplasms in bone marrow trephines. 1069 67

A newborn infant with congenital T cell lymphoblastic leukaemia presented with hepatosplenomegaly and pancytopenia at birth and died on the 21st day of multi-organ failure. Biopsy and necropsy examination showed extensive atypical lymphoid infiltrates in the lungs, liver, spleen, kidneys, lymph nodes, and bone marrow. Immunohistochemically, the lymphoid cells were TdT+, CD3+, CD45RO+, and CD10-, CD79a-, CD20-. Genotypic analysis using polymerase chain reaction showed T cell receptor gamma chain gene rearrangement and absence of immunoglobulin heavy chain gene rearrangement. This appears to be the first documented case of congenital T cell lymphoblastic leukaemia. The case had unusual histological and immunogenotypic features, disseminated early, and pursued a highly aggressive course. Consideration of the diagnosis is of paramount importance. The immunophenotypic studies and molecular characterisation of such congenital leukaemias are critical in arriving at a definite diagnosis.
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PMID:Congenital acute T lymphoblastic leukaemia: report of a case with immunohistochemical and molecular characterisation. 1076 33

The Shwachman-Diamond syndrome (SDS) is a rare congenital disorder for which inheritance by an autosomal recessive trait has been suggested. Shwachman-Diamond syndrome is defined by exocrine pancreatic insufficiency combined with severe neutropenia. Moreover, SDS patients are at risk to develop neoplastic hematologic diseases. We describe 2 SDS-affected daughters of consanguine parents who were born 1 year apart, at 35 and 36 weeks of gestation, and who died at the age of 4 and 3.5 months, respectively, due to respiratory infections. Histologic bone marrow evaluation of the second-born child revealed a diffuse proliferation of immature B cells, which comprised 40% of the total cellularity. These cells were identified as precursor B cells by immunophenotyping studies (CD79a(+)/CD10(+)/CD20(-)/CD22(-)/CD34(-)/ terminal deoxynucleotidyl transferase(-)). Molecular determination of the immunoglobulin heavy-chain gene status did not reveal clonality. The emergence of this peculiar B-cell population was interpreted as a marked increase of hematogones. Although the clinical significance and the exact function of hematogones is still obscure, they may play a critical regenerative role in the regulation of hemopoiesis, but without malignant potential in SDS. Immunophenotyping and molecular studies, therefore, have potential value in the differential diagnosis of primary bone marrow failures. This report adds SDS to the spectrum of conditions in which a prominent number of hematogones may be observed.
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PMID:Emergence of an unusual bone marrow precursor B-cell population in fatal Shwachman-Diamond syndrome. 1097 44


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