Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell-surface expression of the MIC2 antigen defined by the monoclonal antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus, and peripheral blood (PB) using multiparameter flow cytometry and cell sorting. In contrast to preceding reports, we found that the MIC2 antigen is not restricted to T cells and monocytes. We show that it is also expressed in the B cell and in the granulocytic lineage, the levels of expression being related to distinct maturational stages. CD34+ cells of BM were found to express the antigen at high levels. Along the granulocytic maturation pathway from CD34+CD33+ blasts to mature granulocytes, MIC2 densities appeared progressively reduced with a considerable decline at the myelocyte stage. In B lymphopoiesis, the earliest CD34+ CD10+ B-cell precursor (BCP) cells, further subdivided by expression of CD19, displayed the highest MIC2 density of BM leukocytes. All later BCP stages showed lower MIC2 expression levels, with a remarkable reduction concomitant with loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a subsequent slight upregulation along with maturation to CD10-CD20high surface mu-chain+ BCPs. The brightest MIC2 expression of all cells tested was displayed by the most immature thymic T-lineage cells characterized by the antigenic profile CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak CD8-or weak. Common thymocytes stained slightly less intense with 12E7, whereas all subsequent stages of T-lineage cells in thymus, PB, or BM showed markedly reduced MIC2 levels. Mature peripheral CD4+ as well as CD8+ T cells displayed a bimodal distribution of MIC2. In the CD4+ population, the distinct MIC2 levels were related to the well-studied functional subdivision by differential expression of CD45 isoforms, the helper-inducer/memory subset showing higher MIC2 expression than helper-suppressor/naive CD4+ T cells. Similarly high MIC2 densities were found on CD16+ natural killer cells and on CD14+ monocytes, whereas mature peripheral B cells exhibited low or intermediate expression, and granulocytes exhibited no or only dim expression. These results document that the MIC2 antigen (1) is expressed on all leukocyte lineages; (2) is differentially expressed during T- and B-lymphoid, as well as granulocytic maturation; (3) shows highest expression in the most immature lymphocytic and granulocytic developmental stages; and (4) is also differentially expressed on functional T-cell subsets. We speculate that these observations imply a functional significance of MIC2 in the network of hematopoietic adhesion pathways.
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PMID:Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood. 750 50

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

In lymphoproliferative diseases of the skin, DC have a key role in T- and B-cell homing. Furthermore, DC alterations may have a pathogenic role in the natural history of specific disorders, either in the neoplastic lymphoid cell progression or in antitumoral lymphocyte reaction. Finally, the morphoantigenic and topographic features of DC may have diagnostic and histogenetic relevance in specific conditions. In CTCL, dermal CD1a+ DC ("indeterminate cells") seem to play a significant role in the neoplastic progression of MF, whereas the possible pathogenetic role of specific alterations of epidermal LC is yet to be proven. Recently, a possible implication of DD (resident, perivascular factor XIIIa+/CD1a- DC) in the pathogenesis of MF has been also suggested. The presence and possible significance of DC in CTCL non-MF are presently poorly studied. At present, DC number, distribution, and phenotype seem possibly useful in the differential diagnosis between CTCL and pseudo-CTCL, but this hypothesis has to be adequately confirmed. CBCL has been recently proposed as a unique type of clinically low-grade lymphoma, namely, skin-associated lymphoid tissue (SALT)-related B-cell lymphoma. Both SALT- and mucosa-associated lymphoid tissue (MALT)-related B-cell lymphoma share with a peculiar nodal lymphoma of follicle mantle origin (parafollicular-monocytoid lymphoma) the nonaggressive clinical behavior and the uniform phenotype (CD5-, CD10-) and genotype (lack of bcl-2 gene rearrangement) of neoplastic B cells, despite the wide variability of cytomorphologic appearances. The putative origin of CBCL is further supported by the typical CD14-, nerve growth factor receptor (NGFr)+ immunophenotype of DRC. Moreover, the immunophenotype and architectural fashion of DRC are interesting clues to the differentiation between neoplastic and true reactive folliclelike nodules and may be of help in the differential diagnosis between CBCL and B-cell pseudolymphoma as well as in the correct interpretation of lesions showing monoclonal proliferations of B cells accompanied by polyclonal follicular reactions.
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PMID:Dendritic cells in T- and B-cell proliferation in the skin. 804 37

Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix-negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease.
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PMID:Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells. 845 72

The immunophenotype of 304 adult lymphoblastic leukemias (> 18 years) diagnosed on the basis of the FAB criteria was determined at the time of diagnosis using a panel of monoclonal antibodies. The series comprised cases diagnosed and immunophenotyped in 43 Italian centers (GIMEMA Cooperative Group) between April 1988 and June 1991. The immunophenotypic characterization consisted of two consecutive steps. The initial screening was based on the reactivity for TdT, HLA-Dr, CD7, CD10, CD13, CD19, CD24, CD33 and CD41. According to the results obtained, the second level of investigation assessed the positivity for intra cytoplasmic (Cy) Ig, CD1a, CD2, CD3, CD4, CD5, CD8 and CD20. Based on the hierarchical expression of the different B- and T-cell related antigens, each case was assigned to a given differentiation stage. B-lineage ALL were classified in five subgroups (B0-B4) and T-lineage ALL in four subgroups (T0-T3). Cases in which the blasts were lymphoid according to the FAB criteria, but expressed myeloid antigens in association with B- and T-lymphoid markers were defined as hybrid leukemias. As expected, CD10+ cases (B2-B3) were the most frequent within the B-lineage ALL (83.2% of cases). CyIg+ (B3) accounted for about 20% of CD10+ ALL. Twenty eight cases (13.4%) were at a pre-cALL stage (B0-B1) and of these, 8 (3.8% of the total series) were positive only for TdT and HLA-Dr (B0). Intermediate and mature thymic phenotypes (T2-T3) were predominant within the T-ALL (67.2%) groups. Five cases, were positive only for TdT and CD7 (CD5+), and classified as T0. 9.2% of cases fulfilled the definition of hybrid leukemia, largely in view of the co-expression of B-lymphoid and myeloid markers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunophenotype of acute lymphoblastic leukemia cells: the experience of the Italian Cooperative Group (Gimema). 847 81

We report a case of CD30 positive anaplastic large cell lymphoma of T-cell phenotype developing in association with long-standing tuberculous pyothorax. Phenotypic analysis showed CD1a-, CD2+, CD3+, CD4+, CD5-, CD8-, CD10-, CD19-, CD20 +/-, CD21-, CD25-, CD56-, T-cell receptor (TCR) alpha/beta antigens-, and HLA-DR+ phenotype. Neither rearrangement of TCR beta and gamma chain genes or of immunoglobulin heavy chain gene was detected in DNA extract from fresh material. The lymphoma cells were also shown to express the latent membrane protein-1 and the Epstein-Barr virus (EBV)-encoded nuclear antigen-2 by immunohistochemistry and EBV-encoded small RNAs by in situ hybridization.
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PMID:Ki-1 (CD30) positive anaplastic large cell lymphoma of T-cell phenotype developing in association with long-standing tuberculous pyothorax: report of a case with detection of Epstein-Barr virus genome in the tumor cells. 852 14

Hematopoietic cells and their progenitors play important roles in human cytomegalovirus latency and reactivation. Latent infection has been evaluated in defined populations of myeloid-lineage-committed progenitor cells coexpressing CD33 and CD15 or CD33 and CD14 along with the dendritic cell markers CD1a and CD10. These CD33+ cell populations were found to support latency and expression of viral latency-associated transcripts and to undergo reactivation of productive viral replication when differentiated in the presence of human fibroblasts. Reactivation was also observed when myeloid cells were carried in the presence of fibroblast-conditioned medium or medium supplemented with certain cytokines (interferon gamma, tumor necrosis factor alpha, interleukin 4, or granulocyte-macrophage colony-simulating factor), suggesting that cell differentiation pathways act as determinants of reactivation. More primitive CD34+ hematopoietic cells were also found to be susceptible to viral infection and latency was maintained as these cells differentiated into CD33+-lineage-committed populations. Between 0.01% and 0.001% of CD33+ CD14+ or CD33+ CD15+ bone marrow mononuclear cells isolated from naturally infected individuals were found to express latent transcripts. Thus, cytomegalovirus is carried within a small percentage of myeloid and dendritic cell progenitors in the healthy seropositive host. Virus reactivation may be triggered by factors associated with the inflammatory response.
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PMID:Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. 952 Apr 71

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

At the ISAC 2000 Congress, the Clinical Cytometry Society organized a meeting of international experts to reach consensus on the minimum number of antibodies required for a full evaluation of hematologic and lymphoid neoplasias. A questionnaire was distributed prior to the meeting to numerous experts from US and European institutions and 13 responses were received. At the meeting, 25 individuals, including most of those who returned responses, participated in the discussions and voted on the issues presented. In chronic lymphoproliferative disorders (CLD), 9 antibodies (anti-CD5, CD19, kappa, lambda, CD3, CD20, CD23, CD10, and CD45) were deemed essential for initial evaluation by 75% of the participants. There was near unanimity that additional markers (selected from CD22, FMC7, CD11c, CD103, CD38, CD25, CD79b and heavy chains for B-cell disorders, and CD4, CD7, CD8, CD2, CD56, CD16, TCRa/b, and TCRg/d for T-cell disorders) would be needed to fully characterize CLD, although not every marker would be useful in all cases. Tissue lymphomas were believed to be similar to CLD, needing a minimum of 12--16 markers. However, for some cases, CD30, bcl-2, TdT, CD71, CD1a, and CD34 were cited as useful by the participants. Markers mentioned for plasma cell disorders included kappa, lambda, CD38, CD45, CD56, CD19, CD20, CD138, and heavy chains. Of 17 voting participants, 16 agreed that between 5 to 8 markers would be essential reagents for plasma cell disorders. For acute leukemia (AL), 10 markers (CD10, CD19, CD13, CD33, CD34, CD45, CD7, CD14, CD3, and HLADR) were considered essential by 75% of participants for initial characterization of the leukemia lineage. Most (>75%) agreed that at least one more B (CD20, CD22, CD79a, IgM), T (CD1a, CD2, CD4, CD5, CD8), myeloid (CD11b, CD15, CD64, CD117, myeloperoxidase), erythroid (CD36, CD71, glycophorin A), and megakaryocytic (CD41, CD61) reagents should be included in the essential panel. However, there was no agreement as to which was optimal. Thus, approximately 13--15 of those reagents would be considered essential in all cases of AL, whereas others (CD16, CD56, CDw65, TdT, and cytoplasmic CD3) were mentioned as useful in some cases. Almost all voting participants believed that the appropriate number of markers for complete characterization of AL would average 20--24. The majority of the responders (11 of 13) indicated that fewer reagents could be used in monitoring or staging patients with previously characterized disease, but not all ventured a specific number of reagents. From the above results, we conclude that the phenotypic analysis of hematologic and lymphoid neoplasia requires a rather extensive panel of reagents. Supplementary reagents might even be necessary if they prove to become relevant for diagnostic purposes. Reducing the number of antibodies could significantly compromise the diagnostic accuracy, appropriate monitoring, or therapy of these disorders.
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PMID:Optimal number of reagents required to evaluate hematolymphoid neoplasias: results of an international consensus meeting. 1124 3

The identification of immunophenotypic markers with restricted expression has long been a critical issue in diagnostic and therapeutic advances for acute leukemias. We previously developed a monoclonal antibody against a new thymocyte surface antigen, JL1, and showed that JL1 is expressed in the majority of acute leukemia cases. In this study, using multiparameter flow cytometric analyses, we found that JL1 was uniquely expressed in subpopulations of normal bone marrow (BM) cells, implying the association of JL1 with the differentiation and maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+) AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors, CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell development or after CD1a down-regulation in thymocytes. Despite the highly restricted expression of JL1 in normal BM cells, most of the leukemias express JL1 irrespective of their immunophenotypes. These results indicate that JL1 is not only a novel differentiation antigen of hematopoietic cells, but also a leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate molecule in acute leukemia for the diagnosis and immunotherapy that spares the normal BM stem cells.
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PMID:Expression of leukemia-associated antigen, JL1, in bone marrow and thymus. 1129 May 65


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