Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential of various photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants is discussed in this paper. The results with fluorescent dyes, Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) are detailed. Following photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity towards lymphoid and myeloid neoplastic cells, but had significantly less effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, cALLa positive acute lymphoblastic leukemia (Reh), and diffuse histiocytic B-cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 ug/ml and MC-540 concentrations of 15 to 20 ug/ml, clonogenic tumor cells could be reduced by more than 4 logs, when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells, and on normal marrow myeloid (CFU-GM) precursors, when the drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15-20 ug/ml) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). Using DHE (2.5 ug/ml), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared, following sequential drug and light exposure of cells, while simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. The data from various centers is briefly discussed with special emphasis on clinical trials. Our results provide a useful model for leukemia and lymphoma cells and suggest that these phototherapy experiments can be implemented into clinical trials.
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PMID:Photoradiation methods for purging autologous bone marrow grafts. 213 34

The possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
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PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48

To assess the potential of photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants, we studied normal marrow and tumor cell clonogenicity in response to different light-activated compounds by using the fluorescent dyes dihematoporphyrin ether (DHE) and merocyanine-540 (MC-540). After photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity toward lymphoid and myeloid neoplastic cells but had a significantly lesser effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, CALLA-positive acute lymphoblastic leukemia (Reh), and diffuse histocytic B cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 micrograms/mL and MC-540 concentrations of 15 to 20 micrograms/mL, clonogenic tumor cells could be reduced by more than 4 logs when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells and on normal marrow myeloid (CFU-GM) precursors when drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15 to 20 micrograms/mL) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). When using DHE (2.5 micrograms/mL), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared after sequential drug and light exposure of cells, whereas simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. In summary, our results indicate the usefulness of various photoradiation models for the ex vivo treatment of leukemic and lymphomatous bone marrow autografts.
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PMID:Photoradiation models for the clinical ex vivo treatment of autologous bone marrow grafts. 295 18

We have used oligonucleotide probes, based on a portion of the p60v-src autophosphorylation sequence, Glu-Asp-Asn-Glu-Tyr-Thr, to identify and characterize a cDNA from the human T-leukemia cell line, JURKAT. The JURKAT cDNA (designated ptk-JURKAT) was homologous to but distinct from the src, yes and fgr oncogenes, which encode protein-tyrosine kinases (ATP:protein phosphotransferase, EC 2.7.1.37). The ptk-JURKAT cDNA hybridized with a 2.2 kb RNA transcript from JURKAT cells and the human T-cell lymphoma line, MOLT-4, but failed to identify any transcript in two human B-cell lymphoma lines or a human erythroid-myeloid leukemia line, K562. Recently the nucleotide sequence has been established for the murine lymphocyte protein tyrosine kinase, p56LSTRA. The ptk-JURKAT cDNA appears to encode the human homolog of p56LSTRA.
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PMID:Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA. 348 86

The epitopes Tn and sialosyl-Tn are expressed on erythrocytes of individuals with a very rare blood group, who often suffer from "Tn syndrome." We surveyed expression of Tn and sialosyl-Tn in normal blood cells, malignant transformed cells, and progenitor stem cells from bone marrow (BM). An anti-Tn antibody, IE3, and an anti-sialosyl-Tn antibody, TKH2, were used in this study. TKH2 reacted with erythroblasts, B cells, and a subset of CD4+ cells; but not with erythrocytes. Erythroblastic cell lines (K562, HEL, and UT7/EPO) and B-cell lines (Daudi, Raji, and B-cell lines transformed by Epstein-Barr virus) showed reactivity to TKH2. Similar results from the reactivity of TKH2 with transformed cells from leukemia patients and lymphoma patients were obtained; TKH2 reacted with blasts from erythroleukemia (M6; for 4 of 4 cases) and with lymphocytes from B-cell chronic lymphocytic leukemia (3 of 3), B-cell lymphoma (5 of 5), and CD4+ adult T-cell leukemia (4 of 4), but did not react with blasts from acute myeloid leukemia (M0 to M5; 0 of 22) or acute lymphoid leukemia (B-lymphoid leukemia, 0 of 11; T-lymphoid leukemia, 0 of 2; undifferentiated leukemia, 0 of 1). IE3 did not react with all of the tested cells. CD2-CD19-TKH2+ normal BM cells (BMC) contained blasts and various maturation stages of erythroblasts. The TKH2+ cells produced a large number of colony-forming unit-erythroid (CFU-E) colonies, whereas they produced a small number of burst-forming unit-erythroid colonies and CFU-granulocyte-macrophage colonies. CD34+ normal BMC did not express Tn and sialosyl-Tn. These findings suggest that sialosyl-Tn expresses in CFU-E to erythroblasts.
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PMID:Expression of sialosyl-Tn in colony-forming unit-erythroid, erythroblasts, B cells, and a subset of CD4+ cells. 790 75

We diagnosed a probable fludarabine-induced secondary MDS approximately 18 months after treatment of a low grade non-Hodgkin's lymphoma. After diagnosis of a B-cell lymphoma composed of relatively small cells, fludarabine was administered between May and October, 1997, to a 64-year-old female patient. In December 1998, a mild bicytopenia was present with a leukocyte count of 3800/microl and platelets of 142000/microl. The white cell differential count was normal. The hemoglobin level was normal, but MCV was elevated. Bone marrow cytology revealed normal cellularity with dyserythropoiesis and dysmegakaryocytopoiesis. PAS staining showed scattered positivity in early erythroid cells. In 12 of 20 mitoses, the karyotype showed complex rearrangements, described as 46,XX,t(4;11)(q23?24;q13),del(5q),del(7)(q22),+mar[8]/45,-3. A diagnosis of treatment-related MDS was made. While there was no evidence of bone marrow infiltration by the lymphoma, CT scans demonstrated paraaortic lymph nodes up to 10 cm in diameter. After one course of CHOP chemotherapy, prolonged bone marrow aplasia and septic complications occurred. Chemotherapy was abandoned and Rituximab was administered. In July and November, 1999, bilateral pneumonia and urinary tract infection, respectively, were treated with antibiotics. NHL was in complete remission, but peripheral blood counts deteriorated markedly, and transfusions of packed red cells had to be started in November, 1999. The suspicion of leukemic transformation could not be confirmed because the patient declined further bone marrow biopsies. In December, 1999, the patient died from pneumonia.
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PMID:Secondary myelodysplastic syndrome after fludarabine therapy of a low-grade non-Hodgkin's lymphoma. 1113 66

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.
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PMID:Epstein-Barr virus associated diffuse large B-cell lymphoma complicated by autoimmune hemolytic anemia and pure red cell aplasia. 1169 22

When cells were incubated in the presence of both interferon-gamma (IFN-gamma) and all-trans retinoic acid (ATRA), the concentration of IFN-gamma required to induce apoptosis of B-cell lymphoma cells was much lower than that required for myeloid or erythroid cell lines. The concentration of IFN-gamma that effectively inhibited the proliferation of BALM-3 cells was 1/40 of that required for BALM-1 cells. STAT-1 phosphorylation, IRF-1 mRNA and protein expression and RAR-beta expression were enhanced to a greater degree in BALM-3 cells treated with IFN-gamma and ATRA than in BALM-1 cells treated with IFN-gamma and ATRA, suggesting that these IFN-gamma related genes were involved in the induction of apoptosis of BALM-3 cells.
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PMID:Human B-cell lymphoma cell lines are highly sensitive to apoptosis induced by all-trans retinoic acid and interferon-gamma. 1219 70

Two unusual cases of large B-cell lymphoma with predominant splenic and bone marrow (BM) involvement and similar clinical and histopathologic features are described. Both patients presented with nonspecific constitutional symptoms, unexplained cytopenias, and splenomegaly. Splenectomy revealed diffuse red pulp involvement by large B-cell lymphoma. The perisplenic lymph nodes were also involved diffusely with effacement of normal nodal architecture, excluding a diagnosis of intravascular large B-cell lymphoma. BM biopsies revealed striking erythroid hyperplasia without overt morphologic evidence of involvement by lymphoma. Immunoperoxidase staining of the marrow biopsies with antibodies to CD20 and erythroid-associated antigens revealed involvement by large B-cell lymphoma morphologically resembling the early pronormoblasts. In both cases there was prominent, but not exclusive, intravascular/intrasinusoidal lymphomatous marrow infiltration. These cases represent an unusual variant of large B-cell lymphoma with distinctive patterns of splenic and BM involvement. Furthermore, they underscore the difficulties in identifying intrasinusoidal marrow infiltration by lymphoma in H&E-stained biopsy slides and demonstrate that this pattern of marrow infiltration may be seen in cases of large B-cell lymphoma distinct from the intravascular variant.
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PMID:Diffuse large B-cell lymphoma with distinctive patterns of splenic and bone marrow involvement: clinicopathologic features of two cases. 1549 60

The long form of B-cell lymphoma-x (Bcl-x(L)), an outer mitochondrial membrane protein, has been proposed to mediate the antiapoptotic action of erythropoietin on erythroid progenitor cells and to be necessary for heme synthesis in erythroblasts. Mice with conditional knockout of Bcl-x(L) (conditional bcl-x(-/-) mice) develop severe anemia that has been attributed to hemolysis and is accompanied by splenomegaly. We characterized further the anemia of conditional bcl-x(-/-) mice and investigated the role of Bcl-x(L) in the action of erythropoietin and in heme synthesis. We analyzed peripheral blood cells and cultured splenic erythroblasts of conditional bcl-x(-/-) mice and littermates that were rendered anemic by bleeding. Although they had massive splenic erythroblastosis, conditional bcl-x(-/-) mice had decreased circulating reticulocytes compared to littermates even prior to bleeding the littermates. Compared to erythroblasts of bled littermates, bcl-x(-/-) erythroblasts cultured with erythropoietin underwent apoptosis during the later, hemoglobin-synthesizing stages of differentiation. The bcl-x(-/-) erythroblasts synthesized heme, but at reduced rates compared to bled littermate erythroblasts. When cultured without erythropoietin, bcl-x(-/-) erythroblasts underwent apoptosis at early stages of differentiation, prior to hemoglobin synthesis. Bcl-x(L) is not required for heme synthesis and does not mediate the antiapoptotic effects of erythropoietin, but it prevents ineffective erythropoiesis due to apoptosis in late-stage, hemoglobin-synthesizing erythroblasts.
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PMID:Bcl-x(L) prevents apoptosis of late-stage erythroblasts but does not mediate the antiapoptotic effect of erythropoietin. 1589 20


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