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)

The circulating lymphoid cells of eight consecutive untreated infants with severe combined immunodeficiency disease (SCID) with B cells were analyzed for surface marker expression and function. The B cells of these children expressed sIg, HLA-DR, CD19 (B4), CD20 (B1), CD21 (B2), Leu-8, and lacked expression of CD10 (CALLA), as do normal peripheral blood B lymphocytes. SCID B cells also expressed antigens that are normally absent or present on only a minor subset of circulating adult B lymphocytes, including CD1c (M241), CD38 (OKT10), CD23 (PL13), with or without concomitant CD5 (Leu-1) expression. The B cells of these children were capable of proliferating in vitro when stimulated with Staphylococcus aureus Cowan I. However, in the presence of pokeweed mitogen, S. aureus Cowan I, and normal T cells, the sIg+ cells of these children produced only IgM. Studies performed on normal B cells obtained from cord blood, young children, and adults reveal that whereas cord blood B cells are predominantly CD1c, CD38, and CD23 positive, B-cell expression of these antigens decreases with age. Cord blood B cells, similar to SCID B cells, produce only IgM when stimulated in vitro with pokeweed mitogen and S. aureus Cowan I. Based on these observations, we hypothesize that SCID B cells represent a population of B cells present during normal B-cell ontogeny which becomes a minor subset when an individual develops full immunologic competence.
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PMID:Characterization of B cells in severe combined immunodeficiency disease. 267 Aug 51

A new lymphoma cell line, designated SUBL, was established from a Japanese patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during FK 506 therapy after liver transplantation. This cell line has undergone 80 passages over a period of 22 months. The cultured cells were positive for CD19, CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The EBV genome was detected in the original tissue and the cell line by the in situ hybridization method. These data indicate that this cell line represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful heterotransplantation to mice with severe combined immunodeficiency (SCID). Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line will provide a useful in vitro system to study the relationship between chromosomal abnormalities and the activation of cellular oncogenes.
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PMID:Establishment of Epstein-Barr virus-associated lymphoma cell line SUBL with t(2;3)(p11;q27) from a liver transplant patient. 750 36

Human multiple myeloma (MM) xenografts have been difficult to establish in athymic mice. We examined the feasibility of establishing human MM xenograft growth in SCID mice following subcutaneous (sc) injection of 1-2 x 10(7) cells from the human plasma cell dyscrasia (PCD) cell lines RPMI 8226 and ARH-77. SC tumors emerged in 67% (6/9) of RPMI 8226- and 6 of 6 ARH-77-injected mice after a latency period of 9-54 days, and reached 19-35 mm in diameter before the mice were sacrificed. RPMI 8226 and ARH-77 primary tumor DNA hybridized positively with the human genome probe Alul-(Blur8), confirming successful engraftment of the human MM cell lines. The RPMI 8226 xenografts comprised predominantly of plasmacytoid cells that expressed the relevant cytoplasmic immunoglobulin (cIg) light chain isotype. Xenografted RPMI 8226 cells also expressed CD10 (CALLA; 44% reactive cells), CD38 (OKTIO; 69%), CD5 (49%), and reacted with the MM monoclonal antibody MM4 (39%). Human MM growth appeared to be localized subcutaneously for both RPMI 8226 and ARH-77 xenografts. There were no detectable metastatic foci in kidney, brain, heart, or bone marrow. Whereas diffuse plasma cell infiltrates were observed in spleen, GI tract, and lung biopsies of tumor-bearing mice, these infiltrates were of host origin according to immunophenotyping and DNA analyses. Neither the originating RPMI 8226 line nor its SCID mouse xenograft expressed Epstein Barr virus (EBV) genome sequences. These observations indicate that both EBV- (RPMI 8226) and EBV+ (ARH-77) cell lines can be successfully propagated in SCID mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterotransplantation of human multiple myeloma cell lines in severe combined immunodeficiency (SCID) mice. 839 Dec 43

The establishment of an in vivo animal model system for infant acute lymphoblastic leukemia (ALL) would allow the testing of new agents against primary leukemic cells from infant ALL patients. We have demonstrated previously that growth of B-lineage leukemic cells in mice with severe combined immunodeficiency (SCID) was a significant prognostic factor for children with high risk ALL. We now have examined the significance of this prognostic variable for 13 infants with newly diagnosed ALL treated at participating institutions of the Children's Cancer Group (CCG). Chromosomal translocations were detected in 10/12 evaluated cases, including five with t(4;11), one each with t(7;9) and t(7;11), t(1;19), and t(9;22), and two with t(11;19). Twelve of the thirteen infants with ALL achieved remissions following induction chemotherapy. Primary leukemic cells from 8 of the 13 infants caused overt leukemia in SCID mice. Among these 8 SCID+ infants, 7 were CD10- and seven had cytogenetic or molecular evidence of an 11q23 rearrangement. Six of the 8 SCID+ infants have relapsed; only 2 remain in remission following chemotherapy or bone marrow transplant. However, among the 5 SCID- infants there were also two relapses. These data are suggestive of a poorer outcome for SCID+ infants, but larger numbers of patients must be analyzed to assess their statistical significance. In summary, we have established a SCID mouse model for human infant ALL that will be useful for 1) predicting short-term and long-term outcome of patients, 2) testing pharmacokinetics, efficacy, and toxicity of new agents, and 3) elucidating the in vivo mechanisms of chemotherapeutic drug resistance in infant ALL.
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PMID:Primary blasts from infants with acute lymphoblastic leukemia cause overt leukemia in SCID mice. 971 59

A mantle cell lymphoma (MCL) cell line (JeKo-1) was established from peripheral blood mononuclear cells of a patient with a large cell variant of MCL showing leukaemic conversion. JeKo-1 cells were Epstein-Barr virus negative and showed a B-cell phenotype with IgM+, IgD+, CD3-, CD5+, CD10-, CD19+, CD20+ and CD23-; they overexpressed cyclin D1, Bcl-2, c-Myc and Rb proteins. Bcl-1/J(H) gene rearrangement was confirmed by polymerase chain reaction, although karyotypic analysis showed 40/41 chromosomes devoid of apparent t(11;14)(q13;q32) translocation. JeKo-1 cells were highly tumourigenic in SCID mice.
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PMID:Establishment and characterization of a mantle cell lymphoma cell line. 975 63

The nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenotransplantation model is increasingly utilized to study both human lymphohematopoietic stem/progenitor cells and committed cell types. Human B lymphoid cells develop and proliferate in this model. We found high numbers of CD19+CD5+ B lymphoid cells in the bone marrows and spleens of NOD/SCID mice transplanted with human CD34+ stem/progenitor cells. The CD5+ cells accounted for a particularly large percentage of the B lymphoid cells in the spleens of chimeras analyzed three months after transplantation. CD19+CD5+ cells from all the analyzed chimeras coexpressed HLA-DR, surface IgM, CD20, CD38, CD43, and CD45. However, CD19+CD5+ cells were negative for kappa light chain, CD10, CD11a, CD11b, CD15, CD21, CD22, CD23, CD25, CD34, CD35, CD44, CD62L, CD69, and CD71. Cell surface expression of the lambda light chain, surface IgD, CD9, and CD40 antigens was detected in some but not all chimeras. Thus, the CD19+CD5+ cell population detected in our study has the phenotype of previously described CD5+ B lymphoid cells in humans and other species. The origin and role of the B lymphoid cells which express CD5 cell surface glycoprotein are poorly understood. The malignant cells in B lymphoid chronic lymphocytic leukemia express CD5, and the numbers of CD5+ B lymphoid cells are elevated in several autoimmune conditions. The human-NOD/SCID chimera system may provide an in vivo model to investigate the maturation and development of this cryptic human CD5+ B lymphoid cell subpopulation.
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PMID:Human hematopoietic stem/progenitor cells generate CD5+ B lymphoid cells in NOD/SCID mice. 1052 59

The cytoplasmic spleen tyrosine kinase (SYK) is a key regulator of signal transduction events, apoptosis and orderly cell cycle progression in B-lineage lymphoid cells. Although SYK has not been linked to a human disease, defective expression of the closely related T-cell tyrosine kinase ZAP-70 has been associated with severe combined immunodeficiency. Childhood CD19(+)CD10(-) pro-B cell acute lymphoblastic leukemia (ALL) is thought to originate from B-cell precursors with a maturational arrest at the pro-B cell stage and it is associated with poor prognosis. Since lethally irradiated mice reconstituted with SYK-deficient fetal liver-derived lymphohematopoietic progenitor cells show a block in B-cell ontogeny at the pro-B to pre-B cell transition, we examined the SYK expression profiles of primary leukemic cells from children with pro-B cell ALL. Here we report that leukemic cells from pediatric CD19(+)CD10(-) pro-B cell ALL patients (but not leukemic cells from patients with CD19(+)CD10(+) common pre-pre-B cell ALL) have markedly reduced SYK activity. Sequencing of the reverse transcriptase-polymerase chain reaction (RT-PCR) products of the Syk mRNA in these pro-B leukemia cells revealed profoundly aberrant coding sequences with deletions or insertions. These mRNA species encode abnormal SYK proteins with a missing or truncated catalytic kinase domain. In contrast to pro-B leukemia cells, pre-pre-B leukemia cells from children with CD19(+)CD10(+) common B-lineage ALL and EBV-transformed B-cell lines from healthy volunteers expressed wild-type Syk coding sequences. Examination of the genomic structure of the Syk gene by inter-exonic PCR and genomic cloning demonstrated that the deletions and insertions in the abnormal mRNA species of pro-B leukemia cells are caused by aberrant splicing resulting in either mis-splicing, exon skipping or inclusion of alternative exons, consistent with an abnormal posttranscriptional regulation of alternative splicing of Syk pre-mRNA. Our findings link for the first time specific molecular defects involving the Syk gene to an immunophenotypically distinct category of childhood ALL. To our knowledge, this is the first discovery of a specific tyrosine kinase deficiency in a human hematologic malignancy.
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PMID:Spleen tyrosine kinase (Syk) deficiency in childhood pro-B cell acute lymphoblastic leukemia. 1149 25

The Wayne State University Waldenstrom's Macroglobulinemia xenograft model in mice with severe combined immune deficiency (WSU-WM-SCID) is the only preclinical animal model available for this disease. It is based on a permanent, EBV- IgMlambda cell line (WSU-WM) established from a patient with a 10-year history of Waldenstrom's macroglobulinemia (WM). These cells are CD5(-)CD10(+)CD19(+)CD20(+)CD22(+) and have t(8;14) (q24;32), t(12;17) (q24;q21), 2p-. WSU-WM cells also express DNA topoisomerase II (alpha and beta), and are bcl(2)(+)bcl(XL)(+)bax(-). Although the tumor has aggressive biological behavior with c-myc-IgH rearrangement, it has retained the salient features of WM. The breakpoint on 8q24 is downstream of c-myc exon 3, which is not usual for Burkitt-type breakpoints. WSU-WM cells also express both secretory (s(u)) and membrane (m(u)) IgM mRNA and secrete IgM in culture supernatant. Histiologically, WSU-WM-SCID xenograft tumors have lymphoplasmacytoid morphology. These features indicate biological, but not histological evolution. The WSU-WM-SCID is a model of a more aggressive and resistant WM usually seen toward the late stages of disease. It is, therefore, a particularly useful tool in developing new therapeutic strategies for the more aggressive WM, including targeted therapy, which exploits unique molecular characteristics of tumor cells.
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PMID:The Wayne State University Waldenstrom's Macroglobulinemia preclinical model for Waldenstrom's macroglobulinemia. 1272 Jan 60

Only some acute lymphoblastic leukemia (ALL) cells are thought to be capable of proliferating to maintain the leukemic clone, and these cells may be the most relevant to target with treatment regimens. We have developed a serum-free suspension culture (SC) system that supported growth of B-ALL cells from 33 patients for up to 6 weeks. ALL cells from 28 cases (85%) were expanded in this system, and growth was superior in SC than in long-term bone marrow culture. To characterize ALL progenitors, cells were sorted for expression of CD34 and CD10 or CD19 and the subfractions assayed in SC and in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Cells capable of long-term proliferation in vitro and NOD/SCID repopulation were derived only from the CD34(+)/CD10(-) and CD34(+)/CD19(-) subfractions, and these cells could engraft secondary recipients. The engrafted cells had the same immunophenotype and karyotype as was seen at diagnosis, suggesting they had differentiated in vivo. These results demonstrate that ALL cells capable of long-term proliferation in vitro and in vivo are CD34(+)/CD10(-)/CD19(-). This suggests that cells with a more immature phenotype, rather than committed B-lymphoid cells, may be the targets for transformation in B-ALL.
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PMID:Characterization of acute lymphoblastic leukemia progenitor cells. 1586 24

A novel tumor cell line, denominated F6, was established from mutated human embryonic bone marrow mesenchymal stem cells (MSCs) which were induced by the GM-CSF and IL-4 in vitro. The characteristics of the F6 cell line, such as surface antigens, cell cycle, growth curve, gene expression, morphology, cytogenetics and tumor model were analyzed. The F6 cells were round and grew suspended in a plastic dish. The cell line has a strong self-renewal capability, was positive for CD13, CD29, CD44, but negative for CD1alpha, CD3, CD10, CD14, CD23, CD33, CD34, CD38, CD41, CD45, CD54 and HLA-DR. The surface antigens were lower than those of human embryonic MSCs. The karyotype of F6 cells was abnormal. The cell cycle included: G0/G1 phase, 52.24%; G2/M phase, 8.00%; S phase, 41.76%. After the cells had been passaged serially for more than 17 months (62 passages), their characteristics were still retained. The F6 cells resulted in tumors in SCID nude mice in vivo (8/8) and caused metastasis (3/8). The pathologic examination revealed that the tumor cells extensively invaded surrounding normal tissues such as dermis, muscular tissue, nerve tissue, adipose tissue and lymphoid tissue. F6 cell line, tumor tissues derived from F6 cells and the MSCs expressed different levels of the nucleostemin gene. These findings suggested that F6 may be a novel tumor cell line. It may provide evidence for the theory that cancer originates from stem cells, and may be useful for the investigation on safety of human MSCs in the clinical application.
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PMID:A novel tumor cell line cloned from mutated human embryonic bone marrow mesenchymal stem cells. 1528 28


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