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)

A 31 year-old male who was treated with radiation under the diagnosis of malignant lymphoma was admitted to our hospital because of systemic erythema and tumor of bilateral upper arms in October, 1987. Leucocyte count of peripheral blood showed 4,400/microliters with 36% leukemic cells and bone marrow was hypercellular with 85.6% leukemic cells. Leukemic cells were negative for peroxidase reaction and lineage specific monoclonal antibodies such as CD3, CD4, CD8, CD10, CD19 and CD20. T cell receptor (TCR) delta gene was rearranged but TCR beta, TCR gamma and immunoglobulin (Ig) genes were in germline configuration. He was treated with combination regimen of doxorubicin, vindesine, prednisolone and L-asparaginase, and complete remission was obtained. These observations suggest that TCR delta gene rearrangement is useful for determination of clonality in cases without rearrangements of the other TCR and Ig genes.
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PMID:[T cell receptor delta chain gene rearrangement in acute unclassified leukemia]. 260 18

We have studied the immunophenotypic and genotypic features in 35 infants aged less than 1 year with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL). A CD10 (common ALL antigen)-negative, CD19-positive pre-pre-B ALL phenotype was observed in 24 infants. Seventeen of them had blast cells coexpressing myeloid-associated markers such as CD15A (VIM-D5, MZ17) and/or VIM-2, but neither myeloperoxidase nor platelet peroxidase was detected in five of these cases analyzed by electron microscopy. Five patients showed a typical common ALL, five a pre-B ALL phenotype, and one infant was unclassifiable by surface-marker and morphologic analysis. Cytogenetic data, available in 21 of these patients, revealed chromosomal abnormalities involving 11q23 in 10 infants with a CD10-negative pre-pre-B ALL. Immunoglobulin (Ig) and T cell receptor (TCR) gamma, beta and delta gene analysis of 31 infants showed Ig heavy-chain gene rearrangement in all but one patient with evidence for clonal evolution in six and kappa-light-chain rearrangement in three infants. TCR beta-chain and TCR gamma-chain rearrangement occurred in six and five patients respectively, while TCR delta-chain rearrangement was identified in 15 patients. Our data indicate that ALL in infancy may present with heterogeneous immunophenotypic and genotypic features. The high frequency of coexpression of B-lineage and myeloid surface markers as well as of chromosomal rearrangement involving 11q23 suggests that the clonogenic cell of infant ALL may relate to a multipotent progenitor cell in most cases.
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PMID:Phenotypic and genotypic heterogeneity in infant acute leukemia. I. Acute lymphoblastic leukemia. 272 59

Leukemic blasts from 40 consecutively admitted adults with untreated acute lymphoblastic leukemia (ALL) were examined for myeloid surface antigen expression. Of these, 14 (35%) were reactive with one or more myeloid monoclonal antibodies. Each example of myeloid surface antigen-positive (My+ ALL) met the standard morphologic and cytochemical criteria for ALL. In addition, none of the 13 samples studied for ultrastructural evidence of myeloperoxidase met the criteria for acute myelocytic leukemia (AML). All patient samples reacted with lymphoid monoclonal antibodies: CD10+ (8 patients), CD19+ CD10- (2 patients), T cell+ (2 patients), and T cell+ CD10+ (2 patients). Coexpression of myeloid and lymphoid determinants was established by two-color immunofluorescence studies using flow cytometry in five of five samples analyzed. Cytogenetic abnormalities that have been associated with myeloid and mixed leukemias were common, including t(9;22), 7q-, abnormalities of 11q with or without a translocation, 20q-, and -5. Blasts from seven patients were studied at the molecular level. Immunoglobulin heavy chain gene rearrangements were detected in five of five samples with B cell+ T cell- phenotypes. One sample that was T cell+ CD10+ was germline for the immunoglobulin heavy chain and the T cell receptor gamma- and beta-chain genes. The other patient with T cell+ CD10+ blasts relapsed with AML following allogeneic bone marrow transplantation. The leukemia cells at the time of diagnosis and the cells at relapse demonstrated similar cytogenetics and the same immunoglobulin gene rearrangement, suggesting a clonal relationship. As a group, the My+ ALL patients had a significantly decreased complete remission rate when compared to My- ALL patients. Further studies at the molecular level will be required to determine the significance of karyotype abnormalities in My+ ALL.
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PMID:Myeloid surface antigen-positive acute lymphoblastic leukemia (My+ ALL): immunophenotypic, ultrastructural, cytogenetic, and molecular characteristics. 281 78

We determined the configuration of the genes for the beta (T beta) and gamma (T gamma) chains of the T cell receptor in DNA from 100 consecutive cases of B cell lymphoma and B cell chronic lymphocytic leukemia (B-CLL), and compared the findings with those in 18 T cell neoplasms. In 7 of the 100 B cell specimens, a single nongermline band was detected after digestion with the restriction enzyme BamHI, but the rearrangement could be confirmed with a second restriction enzyme in only two. The B cell fragments were small in size and of limited size diversity when compared with the T cell cases, and germline bands of equal intensity were present. A rearrangement of the T gamma gene was never seen in a B cell sample. In contrast, T cell specimens usually rearranged both alleles of T beta (15 of 18), the rearrangement could be confirmed with a second restriction enzyme (17 of 18), both alleles of the first constant region gene segment of T beta always underwent either rearrangement or deletion, and the T gamma gene was also rearranged or deleted (17 of 18). We conclude that ordered rearrangement of the T cell receptor is a rare event in B cell lymphoma and B-CLL. T cell receptor gene studies allow B and T cell lymphomas to be distinguished from each other and from common acute lymphoblastic leukemia antigen-positive non-T, non-B acute lymphoblastic leukemia.
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PMID:Rearrangement of the genes for the beta and gamma chains of the T cell receptor is rarely observed in adult B cell lymphoma and chronic lymphocytic leukemia. 282 Oct 76

A novel proteinase, termed human T cell-associated serine proteinase (HuTSP), has been highly purified from a human CD8+ T lymphocyte clone. By using a panel of chromogenic model peptide substrates the enzyme was found to specifically recognize L-arginine and to cleave Tos-Gly-Pro-Arg-nitroanilide with high efficiency at a pH optimum of 10.5-11. Exposure to class-specific proteinase inhibitors revealed that HuTSP is a serine endopeptidase. The enzyme has a mol. mass of approximately 50 kDa (non-reduced) and of approximately 25-30 kDa (reduced) when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting HuTSP to be a disulfide-linked dimer. The enzyme is shown to be inducible by lectin in both CD4+ and CD8+ lymphocytes. Moreover, HuTSP was detected in a number of independent CD4+ and CD8+ T cell clones and was found to be released from effector cells upon ligand binding to the CD3-T cell receptor complex.
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PMID:A novel serine proteinase (HuTSP) isolated from a cloned human CD8+ cytolytic T cell line is expressed and secreted by activated CD4+ and CD8+ lymphocytes. 296 May 46

We have studied the cellular and molecular basis of eight cases of infant null acute lymphoblastic leukemia (ALL). All eight patients were under 9 months of age and presented with leukocyte counts in excess of 60 X 10(9)/L, organomegaly, and in two cases CNS infiltration. Although seven cases were morphologically classified as ALL, one patient had both lymphoid and myeloid features. Phenotypic analysis of leukemic blasts from all patients showed a typical null ALL pattern, ie, CD10 (common ALL antigen)-negative, strongly HLA-DR-positive, and CD19 (B4)-positive. The presence of terminal deoxynucleotidyl transferase (TdT) at presentation was positive in six patients' cells and negative in two. Two patients also expressed the myeloid-associated markers CD33 (MY9) and CD15 (TG1), and coexpression of CD19 and CD33 was confirmed in these two by using dual marker flow cytometry (fluorescence-activated cell sorting). Electron microscopic examination of the same two patients' cells showed the presence of monocytoid blasts that labeled with the pan-B cell antibody B4 (CD19). Short-term culture of one of these patients cells in the presence of phorbol ester resulted in the majority of the cells exhibiting myeloid markers, strong nonspecific esterase positivity, and phagocytic properties. Cytogenetic analysis showed the common feature in 7 of 8 cases to be a break in band 11q23. Molecular analysis of DNA from the blast cells of all eight patients showed rearrangement of the immunoglobulin heavy-chain genes in all cases without, however, any evidence of kappa light-chain rearrangement. T cell receptor genes were present in the germline configuration in all cases. Rearrangements of the c-ets 1 oncogene, which maps to band 11q23, were not detected, thus providing no evidence for involvement of this oncogene in the common disease process. Our data indicate that although infant null ALL may present as a heterogeneous disease the similarity of many features between cases suggests a common derivation from a precursor cell sharing phenotypic and genotypic features of both B and myeloid progenitor cells.
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PMID:Cellular and molecular studies on infant null acute lymphoblastic leukemia. 296 29

We constructed a series of MAb heterodimers consisting of the J5 (anti-common acute lymphoblastic leukemia antigen [CALLA]) antibody and antibodies to a variety of structures present on the surface of activated human T cells, including CD3 antigen (T cell receptor-associated glycoproteins), CD2 antigen (T11/E-rosette receptor), CD25 antigen (IL-2 receptor), and the transferrin receptor. We tested the ability of these heterodimers to direct a CD2 + CD3 + CD8 + CD4 - CD25 + transferrin receptor + MHC-restricted human cytolytic T lymphocyte (CTL) clone to lyse a CALLA + human tumor in vitro. Only heterodimers containing an anti-CD3 antibody or activating antibodies to CD2 could direct the clone to lyse these human tumor targets, even when the clone was additionally activated with anti-CD3 or anti-CD2 antibodies. Our findings may have implications in the design of strategies for the use of such reagents in the treatment of human neoplasia.
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PMID:Requirements for the construction of antibody heterodimers for the direction of lysis of tumors by human T cells. 296 15

Children with ALL diagnosed at less than 2 years of age have a poor prognosis when compared with older children. In an effort to identify biologic features of ALL in children less than 2 that might explain this difference, we performed extensive immunophenotypic and molecular genetic analyses on a series of patients. For comparison purposes patients were divided into four groups: CALLA- (CD10-) infants less than 2 years of age at diagnosis (n = 10), CALLA- children greater than 2 years of age at diagnosis (n = 10), CALLA+ infants (less than 2 years, n = 21) and CALLA+ children (older than 2 years, n = 21). No immunophenotyping differences in CALLA- or CALLA+ subgroups were identified when cases less than 2 were compared with cases greater than 2 years of age at diagnosis. The most interesting results were in the CALLA- group where 94% of the samples expressed the B cell antigen CD19 but 27% co-expressed CD7. Double labeling experiments confirmed leukemic blast cells co-expressed CD19 and CD7. The double-labeled cells represent either leukemic conversion of a precursor cell which has not yet committed to B or T cell lineage or aberrant expression of these antigens. Molecular genetic studies demonstrated that all samples, regardless of the patients' age or immunophenotype, had rearrangement of the Ig heavy chain gene. The most striking molecular results were in CALLA- patients; in patients less than 2 at diagnosis neither the beta- nor the gamma-chain gene of the T cell receptor (TCR) was rearranged, whereas DNA from 5 of 10 patients over the age of 2 demonstrated beta- or gamma-chain TCR gene rearrangements. The percentage of CALLA+ cases under the age of 2 years with rearrangements in TCR genes is less than that found in CALLA+ cases over the age of 2 years. The finding of no TCR rearrangements in CALLA- ALL and a decreased number of gamma-TCR rearrangements in CALLA+ cases under the age of 2 suggest that age may affect TCR gene rearrangements in lymphoblasts. The molecular differences in TCR gene rearrangements do not appear to correlate with the response to therapy.
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PMID:T cell receptor gene rearrangements in B-precursor acute lymphoblastic leukemia correlate with age and the stage of B cell differentiation. 297 89

Philadelphia chromosome-positive (Ph1) acute leukemia is a heterogeneous subset of acute leukemia with a poor prognosis. We studied five patients to determine the potential for phenotypic and molecular heterogeneity. Cellular characterization studies included light myeloperoxidase (L-MPO), terminal deoxynucleotidyl transferase (TdT), ultrastructural MPO (U-MPO), and immunophenotyping by flow cytometry using T11, T3, T4, T8, Leu 1, B1, Leu 12, HLA-DR (la), CALLA (J5), OKM1, My4, My7, My8, My9, and My10. DNA was analyzed for rearrangements of the breakpoint cluster region (bcr), immunoglobulin heavy chain, joining region (JH), immunoglobulin kappa light chain constant region (C kappa), and T cell receptor (TcR beta). RNA dot blots were hybridized by using molecular probes for MPO and TdT. We found that four of five cases were acute mixed-lineage leukemia (AMLL). One patient had acute unclassifiable leukemia. Of the four patients classified as having AMLL, three showed myeloid and lymphoid features, with one patient showing myeloid, T cell, and B cell features. The last case showed T cell and B cell features only. In one patient MPO/RNA was positive in spite of insufficient L-MPO or U-MPO to diagnose acute myelogenous leukemia (AML), thereby suggesting significant MPO gene expression before the production of sufficient MPO protein to meet the French-American-British criteria for AML. Three of the five patients showed rearrangement of bcr (cases 1, 2, and 5). Studies of these five patients support the concepts of molecular and phenotypic heterogeneity in Ph1 acute leukemia, demonstrate a high incidence of AMLL in this subset of acute leukemia, and support the use of lineage-associated molecular probes to define lineage at an earlier stage than previously possible.
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PMID:Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia. 333 95

Clinical and laboratory features of seven patients with acute leukemia associated with the (4;11) chromosome translocation are presented. Leukemic blasts of these patients showed lymphoid morphology in 6 (although 1 was treated for monoblastic leukemia 3 years earlier) and monocytoid morphology in 1, were positive for TdT and HD 37 (CD 19) in 6 patients, whereas weak expression of CALLA was seen in only 1 patient and T-lineage-associated antigens in none. Leukemic blasts from four patients showed the simultaneous expression of B-lymphoid and myeloid antigens, suggesting leukemogenesis in a very early multipotent progenitor cell. In 2 patients an isochromosome of the long arm of No. 7 chromosome was found in the leukemic karyotypes in addition to t (4; 11) (q 21; q 23); in one instance present at diagnosis, in the other one occurring at relapse. In one other patient leukemia karyotype also demonstrated trisomy 8. Leukemic cells of three patients were investigated by molecular genetics and demonstrated immunoglobulin gene rearrangements for the Ig heavy chain sequences but not for the light chain constant regions and T cell receptor sequences. All patients were treated by intensive chemotherapy. Four of the 7 patients are in continuous complete remission. The longest event-free survival time (over 2 1/2 years) was seen in one patient who had also DOWN-syndrome. Including these 7 patients a clinical analysis of 71 patients with t (4; 11) acute leukemia was made, emphasizing the following characteristics at diagnosis: female sex (62%), age under 2 years (49%), leukocyte count over 100 X 10(9)/1 (61%), splenomegaly (80%), CNS-disease (11%). Survival of over 2 years was reported in less than 15% of the patients. It remains to be seen if risk-adapted treatment can alter the course of this early B-precursor acute leukemia with hitherto very bad prognosis.
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PMID:Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases. 349 35


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