35 results on '"Burkitt Lymphoma metabolism"'
Search Results
2. Additional flow cytometric studies for differential diagnosis between Burkitt lymphoma/leukemia and B-cell precursor acute lymphoblastic leukemia.
- Author
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Demina I, Voropayev A, Semchenkova A, Zerkalenkova E, Olshanskaya Y, Samochatova E, Novichkova G, Miakova N, Maschan A, and Popov A
- Subjects
- Adolescent, Burkitt Lymphoma immunology, Burkitt Lymphoma metabolism, Child, Child, Preschool, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Immunophenotyping, Infant, Infant, Newborn, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Prognosis, Burkitt Lymphoma diagnosis, Flow Cytometry methods, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis
- Abstract
The differentiation between Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is sometimes complicated. Laboratory findings that favor BL (e.g., surface expression of μ heavy chain and/or one of the light chains of immunoglobulin, FAB L3 morphology of blasts, MYC gene rearrangements) are not always present simultaneously. Our previous work demonstrated that BL differed from Ig(+) BCP-ALL by expression of Ig and other surface markers. In the current study, we have evaluated additional flow cytometric markers for reliable differentiation between BL and BCP-ALL. Among three studied surface antigens (CD44, CD38, CD58), only CD58 demonstrated significantly higher expression in BL as compared to BCP-ALL. Moreover, BL cases were associated with an increased level of Ki-67 and a higher percentage of cells in the S-phase of cell cycle. These two features reflect an aggressive proliferative potential of BL. Thus, when BL is suspected and results of surface Ig evaluation are controversial, the flow cytometric analysis of CD58, Ki-67 and cell cycle could assist in the differential diagnosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
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3. A case of Burkitt Leukemia: Revisiting the prognostic value of lactate dehydrogenase.
- Author
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Bodrog A, Zhang B, Liu L, Casulo C, and Bennett JM
- Subjects
- Biomarkers, Biopsy, Blood Cell Count, Bone Marrow pathology, Burkitt Lymphoma etiology, Burkitt Lymphoma metabolism, Chromosome Aberrations, Humans, Immunohistochemistry, Immunophenotyping, In Situ Hybridization, Fluorescence, L-Lactate Dehydrogenase metabolism, Male, Middle Aged, Prognosis, Burkitt Lymphoma diagnosis
- Abstract
Competing Interests: Declaration of Competing Interest None.
- Published
- 2020
- Full Text
- View/download PDF
4. Expression of platelet parameters and platelet membrane glycoproteins in childhood Burkitt lymphoma.
- Author
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Asare R, Opoku-Okrah C, Danquah KO, Opare-Sem O, Addai-Mensah O, Gyamfi D, Amponsah FA, Afriyie EY, Duneeh RV, Ofosu DN, and Frimpong M
- Subjects
- Age Factors, Biomarkers, Blood Coagulation Tests, Burkitt Lymphoma complications, Burkitt Lymphoma pathology, Case-Control Studies, Child, Female, Humans, Male, Platelet Activation, Platelet Membrane Glycoproteins metabolism, Blood Platelets metabolism, Burkitt Lymphoma etiology, Burkitt Lymphoma metabolism, Gene Expression Regulation, Neoplastic, Platelet Membrane Glycoproteins genetics
- Abstract
Platelet activation and functional changes in some haematological malignancies have been investigated with little or no known documentation on Burkitt lymphoma (BL). Abnormalities of platelets contribute to either haemorrhage or thrombotic episodes which are life-threatening in patients with BL. Thus, the study aimed at investigating the various platelet indices and platelet membrane glycoproteins in childhood Burkitt lymphoma. Platelet surface membrane glycoproteins (GPIIb/IIIa, P-selectin and GPIV using PAC 1, CD62p and CD36 monoclonal antibodies respectively) and platelet indices (Platelet Count [PLT], Plateletcrite [PCT], Mean Platelet Volume [MPV], Platelet Distribution Width [PDW] and Platelet Large Cell Ratio [P-LCR]) were determined in children with Burkitt lymphoma and healthy children (normal controls) based on flow cytometry and automated blood cell analysis techniques. PLT and PCT were higher in BL cases than in the normal controls with a significant difference in the PLT (P = 0.02). On the contrary, we observed a significant (p < 0.05) lower levels in the other platelet indices (MPV, PDW and P-LCR) in children with BL than the controls. With the exception of CD62 P, the other platelet membrane glycoproteins examined showed a decreased level of expression before and after the addition of an Adenosine -5- diphosphate (ADP) in cases of BL. In addition, PAC-1 was probably known to be associated with Burkitt Lymphoma (Odds Ratio [OR] 6.67, Relative Risk [RR] 3.13, 95% CI 1.06-9.21; p = 0.02). Finally, oral bleeding was observed to be the commonest bleeding episodes associated with childhood BL. Flow cytometry analysis and cell counting techniques of platelet assessment has described the expression of the platelet membrane glycoproteins and parameters in children with Burkitt lymphoma. Thus, children with Burkitt lymphoma tend to show normal to increased level of circulatory platelets but decreased platelet membrane glycoprotein expressions and platelet dysfunction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
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5. Quantitative analysis of CDKN2A methylation, mRNA, and p16(INK4a) protein expression in children and adolescents with Burkitt lymphoma: biological and clinical implications.
- Author
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Robaina MC, Faccion RS, Arruda VO, de Rezende LM, Vasconcelos GM, Apa AG, Bacchi CE, and Klumb CE
- Subjects
- Adolescent, Burkitt Lymphoma genetics, Cell Line, Tumor, Child, Preschool, Cyclin-Dependent Kinase Inhibitor p16 genetics, DNA, Neoplasm genetics, Female, Humans, Male, RNA, Messenger genetics, RNA, Neoplasm genetics, Burkitt Lymphoma metabolism, Cyclin-Dependent Kinase Inhibitor p16 biosynthesis, DNA Methylation, DNA, Neoplasm metabolism, Gene Expression Regulation, Neoplastic, RNA, Messenger biosynthesis, RNA, Neoplasm biosynthesis
- Abstract
CDKN2A is a tumor suppressor gene critical in the cell cycle regulation. Little is known regarding the role of CDKN2A methylation in the pathogenesis of Burkitt lymphoma (BL). CDKN2A methylation was investigated using pyrosequencing in 51 tumor samples. p16(INK4a) mRNA and protein levels were measured using real-time PCR and immunohistochemistry, respectively. CDKN2A methylation was detectable in 72% cases. Nuclear expression of p16(INK4a) was not detected in 41% cases. There was an association between methylation and absence of CDKN2A mRNA (P=0.003). In conclusion, CDKN2A methylation occurs at a high frequency suggesting a role in BL pathogenesis and potential therapeutic implications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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6. High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells.
- Author
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Kano C and Wang JY
- Subjects
- B-Lymphocytes metabolism, B-Lymphocytes physiology, Base Sequence, Burkitt Lymphoma enzymology, Burkitt Lymphoma immunology, Cell Line, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Germinal Center metabolism, Germinal Center physiology, Humans, Molecular Sequence Data, Mutagenesis, Proto-Oncogene Proteins c-bcl-6, Burkitt Lymphoma genetics, Burkitt Lymphoma metabolism, Cytidine Deaminase genetics, Cytidine Deaminase metabolism, Genes, Immunoglobulin, Mutation
- Abstract
Ig gene somatic hypermutation in the germinal center (GC) B cells occurs at C and G at roughly the same frequency. In contrast, there is a 2-fold increase of mutations at A relative to T on the non-transcribed strand of the V genes but it is unclear what triggers such strand bias. Using an efficient mutagenesis system that recapitulates characteristic features of Ig gene hypermutation in the GC B cells, we found that low levels of AID induced similar frequency of mutations at A and T. However, high levels of AID specifically increased mutations at A, but not T, leading to strand bias. These results explain why strand bias of A:T mutations is observed only in the highly mutated V genes but not in the less mutated switch region or the BCL-6 gene. High levels of AID also increased the proportion of transversions at G relative to transversions at C. Our results identify a clue to the strand bias of A:T mutations and provide an in vitro model to elucidate this unsolved mystery in the hypermutation field., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
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7. Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro.
- Author
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Han SS, Son DJ, Yun H, Kamberos NL, and Janz S
- Subjects
- Antigens, Differentiation genetics, Antineoplastic Agents chemistry, Apoptosis drug effects, Burkitt Lymphoma genetics, Burkitt Lymphoma virology, Caspase 3 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Dioxolanes chemistry, E2F1 Transcription Factor genetics, Enzyme Activation drug effects, Gene Expression Regulation, Neoplastic drug effects, Genes, myb, Humans, Inhibitory Concentration 50, NF-kappa B metabolism, Proto-Oncogene Proteins c-myc metabolism, Viral Matrix Proteins genetics, Antineoplastic Agents pharmacology, Burkitt Lymphoma metabolism, Dioxolanes pharmacology
- Abstract
Piperlongumine (PL), a pepper plant alkaloid from Piper longum, kills solid tumor cells in a highly selective, potent fashion. To evaluate whether PL may have similar effects on malignant blood cells, we determined the efficacy with which PL inhibits the B-lymphocyte derived neoplasm, Burkitt lymphoma (BL). Low micromolar concentrations of PL (IC(50) = 2.8 μM × 8.5 μM) curbed growth and survival of two EBV(+) BL cell lines (Daudi, Raji) and two EBV BL cell lines (Ramos, DG-75), but left normal peripheral blood B-lymphocytes unharmed. PL-dependent cytotoxicity was effected in part by reduced NF-κB and MYC activity, with the former being caused by inhibition of IκBα degradation, nuclear translocation of p65, and binding of NF-κB dimers to cognate DNA sequences in gene promoters. In 4 of 4 BL cell lines, the NF-κB/MYC-regulated cellular target genes, E2F1 and MYB, were down regulated, while the stress sensor gene, GADD45B, was up regulated. The EBV-encoded oncogene, LMP-1, was suppressed in Daudi and Raji cells. Considering that NF-κB, MYC and LMP-1 play a crucial role in the biology of many blood cancers including BL, our results provide a strong preclinical rationale for considering PL in new intervention approaches for patients with hematologic malignancies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
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8. Evidence for functional trace amine associated receptor-1 in normal and malignant B cells.
- Author
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Wasik AM, Millan MJ, Scanlan T, Barnes NM, and Gordon J
- Subjects
- Apoptosis drug effects, Blotting, Western, Burkitt Lymphoma pathology, Cell Proliferation drug effects, Cells, Cultured, Dopamine metabolism, Flow Cytometry, Humans, Palatine Tonsil cytology, Palatine Tonsil drug effects, B-Lymphocytes metabolism, Burkitt Lymphoma metabolism, Palatine Tonsil metabolism, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled metabolism
- Abstract
Following the observation that dopaminergic components are present in normal and malignant B cells, we now provide evidence that they additionally express the functionally related trace amine-associated receptor-1 (TAAR1). Immunodetectable TAAR1 was found in lines derived from a broad range of B-cell malignancy; and in tonsillar B cells, particularly when activated. L3055 Burkitt's lymphoma cells were shown to respond to prototypical TAAR1 agonists in cytotoxicity assays with features of apoptotic death evident; normal B cells were somewhat less sensitive to the agonists. These data raise the possibility that TAAR1 may have therapeutic relevance to leukemia, lymphoma, and wider B-cell pathologies., Competing Interests: Conflict of interest None., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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9. 7-b, a novel amonafide analogue, cause growth inhibition and apoptosis in Raji cells via a ROS-mediated mitochondrial pathway.
- Author
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Lin B, Chen Z, Xu Y, Zhang H, Liu J, and Qian X
- Subjects
- Adenine, Antineoplastic Agents chemistry, Burkitt Lymphoma metabolism, Cell Cycle drug effects, Cell Line, Tumor, Cell Survival drug effects, Dose-Response Relationship, Drug, Down-Regulation drug effects, Drug Evaluation, Preclinical, Humans, Mitochondria metabolism, Mitochondria physiology, Models, Biological, Naphthalimides chemistry, Necrosis, Organophosphonates, Signal Transduction drug effects, Signal Transduction physiology, Antineoplastic Agents pharmacology, Apoptosis drug effects, Burkitt Lymphoma pathology, Cell Proliferation drug effects, Mitochondria drug effects, Naphthalimides pharmacology, Reactive Oxygen Species metabolism
- Abstract
Previous studies have shown that 7-b (6-(dodecylamino)-2-(3-(4-methylpiperazin-1-yl)propyl)-1H-benzo-[de]isoquinoline-1,3(2H)-dione), a novel amonafide-based DNA intercalator, was generated as a new anticancer candidate. However, the effects induced by 7-b and the molecular mechanisms involved remain poorly understood in Burkitt's lymphoma. To shed light on these issues, we have investigated the effects of 7-b on proliferation, cell cycle progression, apoptosis activity and oxidative stress levels of lymphoma Raji cells in vitro. Our results showed that 7-b inhibited the proliferation of Raji cells and induced G1 cell cycle arrest in a dose-dependent manner. Moreover, 7-b treatment triggered programmed cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (Δψm). Altogether our results showed that 7-b mediated its growth inhibitory effects on Raji cells via the activation of a ROS-mediated mitochondrial pathway and cell cycle checkpoint signaling pathway which subsequently targeted p21., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
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10. The expression of granulysin in systemic anaplastic large cell lymphoma in childhood.
- Author
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Kitamura N, Katagiri YU, Itagaki M, Miyagawa Y, Onda K, Okita H, Mori A, Fujimoto J, and Kiyokawa N
- Subjects
- Adolescent, Adult, Aged, Antigens, CD genetics, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Burkitt Lymphoma metabolism, Burkitt Lymphoma pathology, Female, Flow Cytometry, Hodgkin Disease metabolism, Hodgkin Disease pathology, Humans, Killer Cells, Natural metabolism, Killer Cells, Natural pathology, Lymphoma, B-Cell metabolism, Lymphoma, B-Cell pathology, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large-Cell, Anaplastic metabolism, Lymphoma, Large-Cell, Anaplastic pathology, Male, Middle Aged, Prognosis, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Young Adult, Antigens, Differentiation, T-Lymphocyte genetics, Burkitt Lymphoma genetics, Hodgkin Disease genetics, Lymphoma, B-Cell genetics, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large-Cell, Anaplastic genetics, RNA, Messenger genetics
- Abstract
The expression of granulysin, a cytolytic protein produced by activated T and NK cells, has been revealed to be correlated with the prognosis of some adult cancer patients. By examination on various childhood lymphoma tissues, we found that granulysin level was especially high in systemic anaplastic large cell lymphoma (ALCL) cases, whereas no close correlation with the expression of CD96, a marker for activated T and NK cells, was observed. We further demonstrated that both ALCL cells in biopsy specimens and cell lines established from ALCL express granulysin, indicating some correlation of granulysin with biological features of ALCL.
- Published
- 2009
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11. Targeting NF-kappaB and induction of apoptosis by novel NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) in Burkitt lymphoma cells.
- Author
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Kimura N, Miyakawa Y, Kohmura K, Umezawa K, Ikeda Y, and Kizaki M
- Subjects
- Burkitt Lymphoma metabolism, Caspase 3 metabolism, Cell Line, Tumor, Cell Proliferation, Enzyme Activation, Humans, NF-kappa B antagonists & inhibitors, Phosphorylation, Apoptosis, Benzamides pharmacology, Burkitt Lymphoma pathology, Cyclohexanones pharmacology, NF-kappa B metabolism
- Abstract
A new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), inhibited proliferation and induced apoptosis in human Burkitt lymphoma, HS-Sultan and Daudi cell lines. The activation of caspase-3 and the cleavage of caspase substrate PARP were observed after treatment with DHMEQ. The induction of apoptosis by DHMEQ was prevented by the pretreatment of Burkitt lymphoma cells with pan-caspase inhibitor, z-VAD-FMK. The expression of anti-apoptotic factors such as IAP-1 and XIAP was suppressed by DHMEQ. Phosphorylation of ERK and JNK was induced by DHMEQ. In conclusion, these results demonstrate that NF-kappaB might be an ideal target to develop for new anti-cancer drugs for Burkitt lymphoma.
- Published
- 2007
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12. The chemosensitivity to therapy of childhood early B acute lymphoblastic leukemia could be determined by the combined expression of CD34, SPI-B and BCR genes.
- Author
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Talby L, Chambost H, Roubaud MC, N'Guyen C, Milili M, Loriod B, Fossat C, Picard C, Gabert J, Chiappetta P, Michel G, and Schiff C
- Subjects
- Anthracyclines administration & dosage, Antigens, CD34 genetics, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Asparaginase administration & dosage, Blast Crisis drug therapy, Blast Crisis genetics, Blast Crisis metabolism, Blast Crisis pathology, Burkitt Lymphoma drug therapy, Burkitt Lymphoma genetics, Burkitt Lymphoma pathology, Child, Child, Preschool, Cortisone administration & dosage, DNA-Binding Proteins genetics, Female, Gene Expression Profiling methods, Humans, Infant, Male, Oligonucleotide Array Sequence Analysis methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Predictive Value of Tests, Proto-Oncogene Proteins c-bcr genetics, Transcription Factors genetics, Vincristine administration & dosage, Antigens, CD34 biosynthesis, Burkitt Lymphoma metabolism, DNA-Binding Proteins biosynthesis, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Leukemic genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Proto-Oncogene Proteins c-bcr biosynthesis, Transcription Factors biosynthesis
- Abstract
We have identified genes differentially expressed in childhood early B acute lymphoblastic leukemia at diagnosis, according to chemosensitivity. Chemosensitive (M1) and chemoresistant (M3) patients present <5% and >25% of residual leukemic blasts at 21 days of treatment, respectively. The expression profiles of 4205 genes for 32 patients included in the FRALLE93 protocol have been determined using microarray. From differential analysis, CD34, SPI-B and BCR distinguished M1 from M3 patients using microarray and RT-PCR data. Linear discriminant analysis (LDA) and cross-validation show that the combined expression of these three genes classify and predict correctly around 90% and 80% of patients, respectively.
- Published
- 2006
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13. Chemokine receptor expression and function in childhood acute lymphoblastic leukemia of B-lineage.
- Author
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Corcione A, Arduino N, Ferretti E, Pistorio A, Spinelli M, Ottonello L, Dallegri F, Basso G, and Pistoia V
- Subjects
- Child, Child, Preschool, Female, Humans, Infant, Male, Receptors, Chemokine classification, Burkitt Lymphoma metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Receptors, Chemokine metabolism
- Abstract
Scanty information is available on chemokine receptor expression and function in childhood B-lineage acute lymphoblastic leukemia (ALL). Thirteen pro-B, 17 early pre-B, 12 pre-B, and 9 B-ALL/Burkitt lymphoma (BL) pediatric cases were tested for CXCR1 to CXCR5 and CCR1 to CCR7 expression. CXCR2, CXCR3, and CXCR4 were expressed in the majority of cases, while the other receptors were variably expressed or absent. CXCR4 mediated chemotaxis of all leukemic cell subtypes. Freshly isolated CCR7(+) early pre-B-ALL cells migrated to CCL19, whereas CCR7(+) pro-B- and pre-B-ALL cells were attracted by CCL19 only following culture with soluble recombinant CD40 ligand.
- Published
- 2006
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14. p15 mRNA expression detected by real-time quantitative reverse transcriptase-polymerase chain reaction correlates with the methylation density of the gene in adult acute leukemia.
- Author
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Matsuno N, Hoshino K, Nanri T, Kawakita T, Suzushima H, Kawano F, Mitsuya H, and Asou N
- Subjects
- Acute Disease, Adult, Bone Marrow Cells metabolism, Bone Marrow Cells pathology, Burkitt Lymphoma metabolism, Burkitt Lymphoma pathology, Cell Lineage, CpG Islands, Cyclin-Dependent Kinase Inhibitor p15, Humans, Leukemia, Myeloid classification, Leukemia, Myeloid metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Reverse Transcriptase Polymerase Chain Reaction, Sequence Deletion, Tumor Cells, Cultured, Burkitt Lymphoma genetics, Cell Cycle Proteins genetics, DNA Methylation, Gene Expression Regulation, Leukemic, Leukemia, Myeloid genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, RNA, Messenger metabolism, Tumor Suppressor Proteins genetics
- Abstract
Cyclin-dependent kinase inhibitor p15 is frequently inactivated by either methylation or deletion in patients with acute leukemia. To examine pathologic and clinical significance of the p15 gene inactivation, we established a quantitative assay of p15 mRNA expression in the bone marrow cells by real-time quantitative reverse transcriptase-polymerase chain reaction. p15 mRNA expression in 14 patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL) well correlated with status of deletion and methylation in the p15 gene analyzed by Southern blotting. Furthermore, two patients with PBC-ALL and 11 acute myeloblastic leukemia (AML) were quantitatively examined for p15 gene methylation using bisulfite genomic sequencing. The data showed that p15 mRNA expression significantly correlated with the CpG island methylation density. Among 108 AML patients, p15 mRNA expression was significantly lower in the myeloid lineage (M1, M2, M3) than the monocytic lineage (M4, M5) (P = 0.0019). Above all, the majority of M3 patients showed low p15 expression compared with M1 and M2 patients (P = 0.029). These observations suggest that quantitative analysis of p15 mRNA will be useful to evaluate transcriptional repression of the p15 gene caused by various degrees of methylation.
- Published
- 2005
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15. Peroxisome proliferator-activated receptor gamma ligands induce growth inhibition and apoptosis of human B lymphocytic leukemia.
- Author
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Zang C, Liu H, Posch MG, Waechter M, Facklam M, Fenner MH, Ruthardt M, Possinger K, Phillip Koeffler H, and Elstner E
- Subjects
- Adolescent, Blotting, Western, Burkitt Lymphoma metabolism, Cell Cycle drug effects, Cell Division drug effects, Cell Line, Tumor, Child, Child, Preschool, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Female, Humans, In Situ Nick-End Labeling, Ligands, Male, Middle Aged, Pioglitazone, Polymorphism, Single-Stranded Conformational, Prostaglandin D2 analogs & derivatives, Receptors, Cytoplasmic and Nuclear drug effects, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors drug effects, Apoptosis drug effects, Burkitt Lymphoma pathology, Prostaglandin D2 pharmacology, Receptors, Cytoplasmic and Nuclear metabolism, Thiazolidinediones pharmacology, Transcription Factors metabolism
- Abstract
This study examined the expression and structural intactness of peroxisome proliferator-activated receptor gamma (PPARgamma) in human acute lymphocytic leukemia (ALL) cells and determined the effect of PPARgamma ligands on growth and apoptosis of these cells. We noted that all lymphocytic leukemia cell lines expressed PPARgamma and no PPARgamma mutations were found in these cell lines as indicated by SSCP analysis. Effect of the PPARgamma ligands on the proliferation, differentiation and apoptosis of B type ALL cells was further examined. Treatment of these cells with the PPARgamma ligands Pioglitazone (PGZ) and 15-deoxy-delta (12,14)-prostaglandin J2 (15d-PGJ2) resulted in growth inhibition in a dose-dependent manner which was associated with a G1 to S cell cycle arrest. However, this effect appeared to be PPARgamma-independent since several PPARgamma antagonists could not reverse this effect. No differentiation was induced by this treatment. Four out of five cell lines underwent apoptosis after culture with the PPARgamma ligands. This effect was partially caspase-dependent because a pan-caspase inhibitor partially reversed this effect. In conclusion, our results suggest that PPARgamma ligands may offer a new therapeutic approach to aid in the treatment of ALL.
- Published
- 2004
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16. Immature B cell malignancies synthesize VEGF, VEGFR-1 (Flt-1) and VEGFR-2 (KDR).
- Author
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El-Obeid A, Sunnuqrut N, Hussain A, Al-Hussein K, Gutiérrez MI, and Bhatia K
- Subjects
- Autocrine Communication, B-Lymphocytes metabolism, Blood Cells pathology, Bone Marrow pathology, Burkitt Lymphoma etiology, Burkitt Lymphoma pathology, Cell Line, Tumor, Cytoplasm chemistry, Humans, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma etiology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, RNA, Messenger analysis, Vascular Endothelial Growth Factor Receptor-1 analysis, Vascular Endothelial Growth Factor Receptor-2 analysis, B-Lymphocytes pathology, Burkitt Lymphoma metabolism, Vascular Endothelial Growth Factor A biosynthesis, Vascular Endothelial Growth Factor Receptor-1 biosynthesis, Vascular Endothelial Growth Factor Receptor-2 biosynthesis
- Abstract
Expression of VEGF and VEGFR support a role for angiogenic pathways in the pathogenesis of some hematological malignances. Our goal was to determine if expression of these angiogenic molecules also extend to childhood precursor B cell acute lymphoblastic leukemia (pre-B ALL). We now show that transcripts of VEGF, and its receptors VEGFR-1 and VEGFR-2 are concomitantly expressed in both ALL cell lines and primary pre-B ALL. Western blot and ELISA consistently detected VEGF protein in the supernatants of the cell lines. Similarly, VEGFR-1 and VEGFR-2 proteins are also detectable by FACS analysis. Interestingly, the expression of the receptors in immature B cells is limited to the intra-cytoplasmic compartment and may suggest either internalization of the receptors or a block in trafficking of the receptor to the surface.
- Published
- 2004
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17. Aberrant expression and localization of the cytoskeleton-binding pp52 (LSP1) protein in hairy cell leukemia.
- Author
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Miyoshi EK, Stewart PL, Kincade PW, Lee MB, Thompson AA, and Wall R
- Subjects
- Actins metabolism, B-Lymphocytes drug effects, B-Lymphocytes metabolism, Blotting, Western, Burkitt Lymphoma metabolism, Calcium-Binding Proteins metabolism, Cell Size drug effects, Cytosol metabolism, Humans, Interferon-alpha pharmacology, Intracellular Fluid metabolism, Leukemia, Hairy Cell pathology, Microfilament Proteins, Microscopy, Confocal, Neutrophils metabolism, Neutrophils pathology, Phosphoproteins biosynthesis, Phosphorylation drug effects, Tetradecanoylphorbol Acetate pharmacology, Tumor Cells, Cultured drug effects, Calcium-Binding Proteins biosynthesis, Cytoskeleton metabolism, Leukemia, Hairy Cell metabolism
- Abstract
Non-retractable cell surface projections and cytoskeleton-mediated functional defects are distinguishing features of both hairy cell leukemia (HCL) and neutrophil actin dysfunction (NAD). These defects in NAD neutrophils are attributed to moderate over-expression of pp52 (LSP1), the F-actin-binding, leukocyte-specific phosphoprotein. Here we report that pp52 is similarly elevated in HCL patient PBMCs. Established HCL cell lines exhibited characteristic morphological features like those of fresh HCL cells and showed elevated pp52 levels. The excess pp52 in these HCL cell lines was selectively associated with the F-actin-rich cytoskeletal arrays in surface projections. Treatments producing radical changes in HCL cell shape also altered pp52 expression and intracellular distribution. Alpha interferon (IFNalpha, used to treat HCL) reduced pp52 levels, normalized intracellular pp52 distribution and reverted HCL cells to rounded B cell morphology. Phorbol ester stimulation rapidly generated hyper-phosphorylated pp52 isoforms which translocated from the cytoskeleton to the cytosol prior to the further elongation of surface spikes. This indicates a direct role for phosphorylation in controlling pp52 interactions with the cytoskeleton. Overall, these findings strongly suggest that elevated pp52 expression and/or selective cytoskeletal association contributes to the distinctive morphology of HCL cells.
- Published
- 2001
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18. Hypermethylation of p16 and p15 genes and RB protein expression in acute leukemia.
- Author
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Guo SX, Taki T, Ohnishi H, Piao HY, Tabuchi K, Bessho F, Hanada R, Yanagisawa M, and Hayashi Y
- Subjects
- Acute Disease, Burkitt Lymphoma genetics, Burkitt Lymphoma metabolism, Burkitt Lymphoma pathology, Carrier Proteins biosynthesis, CpG Islands, Cyclin D1 biosynthesis, Cyclin D1 genetics, Cyclin-Dependent Kinase Inhibitor p15, DNA, Neoplasm chemistry, Humans, Leukemia, Myeloid metabolism, Leukemia, Myeloid pathology, Leukemia-Lymphoma, Adult T-Cell genetics, Leukemia-Lymphoma, Adult T-Cell metabolism, Leukemia-Lymphoma, Adult T-Cell pathology, Loss of Heterozygosity, Molecular Probe Techniques, Neoplasm Proteins biosynthesis, Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Sequence Deletion, Tumor Cells, Cultured, Carrier Proteins genetics, Cell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor p16 biosynthesis, DNA Methylation, DNA, Neoplasm genetics, Gene Expression Regulation, Leukemic, Genes, Retinoblastoma, Genes, p16, Leukemia, Myeloid genetics, Neoplasm Proteins genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Retinoblastoma Protein biosynthesis, Tumor Suppressor Proteins
- Abstract
Both p16 and p15, encoded by genes located on chromosome 9p21, are inhibitors of cyclin-dependent kinases 4/6 (CDK4/6) and upstream regulators of RB function, and set up the RB/p16 tumor suppressive pathway, which is abrogated frequently in human neoplasms, either through inactivation of the RB or p16 tumor-suppressor protein, or alteration of the cyclin D1 or CDK4 oncoproteins. In hematological malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid malignancies, and more particularly to T-cell acute lymphoblastic leukemia (T-ALL). However, in the other subsets of ALL, deletions of p16 and p15 are relatively rare events. To investigate whether these genes are inactivated by methylation of the 5' CpG islands, we examined 35 leukemia cell lines and 29 childhood acute myeloid leukemia (AML) patients by Southern blot, polymerase chain reaction (PCR) and Western blot analyses. We found methylation of p16 in 12 (50%) of 24 ALL cell lines, 5 (50%) of 10 AML cell lines without homozygous deletion of p16, and 11 (38%) of 29 AML patients. Those leukemia cell lines subjected to p16 methylation were found to have lost p16 protein expression. The p15 gene was methylated in 10 (34%) of 29 ALL cell lines, 6 (60%) of 10 AML cell lines without homozygous deletion of p15, and 15 (52%) of 29 AML patients. These results revealed the frequent methylation of p16 and p15 genes in B-ALL and AML despite a low frequency of p16 and p15 deletions and mutations in these leukemias. In the study for expression of RB protein, we found no expression of RB in 4 of 16 leukemia cell lines. Inactivation of the p16 gene was found in all the cell lines with expression of RB. Neither amplification nor rearrangement of cyclin D1 gene was found in any cell lines. These results suggest that inactivation of p16 and p15 genes is one of the most common genetic events in acute leukemia, and plays an important role for the RB/p16 pathway in the pathogenesis of acute leukemia.
- Published
- 2000
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19. Bax:Bcl-2 ratio modulation by bryostatin 1 and novel antitubulin agents is important for susceptibility to drug induced apoptosis in the human early pre-B acute lymphoblastic leukemia cell line, Reh.
- Author
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Wall NR, Mohammad RM, and Al-Katib AM
- Subjects
- Antineoplastic Agents therapeutic use, Bryostatins, Burkitt Lymphoma drug therapy, Humans, Lactones therapeutic use, Macrolides, Oligopeptides therapeutic use, Tumor Cells, Cultured, Vincristine therapeutic use, bcl-2-Associated X Protein, Antineoplastic Agents pharmacology, Apoptosis drug effects, Burkitt Lymphoma metabolism, Burkitt Lymphoma pathology, Lactones pharmacology, Oligopeptides pharmacology, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Vincristine pharmacology
- Abstract
The ratio of Bax to Bcl-2 protein can determine whether cells will die via apoptosis or be protected from it. Reh was found to express a high basal level of Bcl-2 but was lacking of Bax protein expression. Treatment with bryostatin 1 induced a down-regulation in Bcl-2 protein that was not accompanied by an obvious Bax protein induction or apoptosis. These results suggest that a decreased level of Bcl-2 alone in this cell line is not sufficient for apoptosis induction. In an effort to identify the mechanism whereby apoptosis could be induced in this ALL model, we treated Reh cells with three microtubule inhibitors: dolastatin 10, auristatin PE and vincristine, in the presence and absence of bryostatin 1. When used alone, only dolastatin 10 induced apoptosis that was detected morphologically, and by flow cytometry. Western blots revealed that dolastatin 10-induced apoptosis was accompanied by the induction of Bax protein and the reduction in Bcl-2 protein. Auristatin PE and vincristine induced both Bax and Bcl-2 protein, leaving the Bax:Bcl-2 ratio constant. Reh cells pretreated for 24 h with bryostatin 1 followed by dolastatin 10, auristatin PE or vincristine showed significant apoptosis which was accompanied by Bcl-2 protein down regulation and Bax protein up regulation. We conclude that: (1) expression of bax is necessary for apoptosis-induction in this model; (2) a decrease in Bcl-2 level alone is not sufficient and might not be necessary for apoptosis-induction; and (3) the ratio of Bax:Bcl-2 plays a critical role in susceptibility to apoptosis in Reh cells. The results from this study should prove useful in guiding the clinical application of these novel agents in the treatment of acute lymphoblastic leukemia.
- Published
- 1999
- Full Text
- View/download PDF
20. Qualitative and quantitative characterization of Fas (APO-1/CD95) on leukemic cells derived from patients with B-cell neoplasms.
- Author
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Tsuruda K, Yamada Y, Hirakata Y, Sugahara K, Maeda T, Atogami S, Tomonaga M, and Kamihira S
- Subjects
- Apoptosis, Burkitt Lymphoma pathology, Flow Cytometry, Humans, Leukemia, Hairy Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphoma, B-Cell pathology, Multiple Myeloma pathology, RNA, Messenger analysis, fas Receptor genetics, fas Receptor physiology, Burkitt Lymphoma metabolism, Leukemia, Hairy Cell metabolism, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Lymphoma, B-Cell metabolism, Multiple Myeloma metabolism, fas Receptor analysis
- Abstract
Expression density and function of Fas (APO-1/CD95) on malignant B-cells, an antigen thought responsible for abnormal tumor biology, remains to be fully understood. Fifty-five cases with B-cell neoplasms of acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), B-cell malignant lymphoma (ML), and myeloma (MM) were studied for qualitative and quantitative expression and function of Fas using flow cytometry and annexin-V staining methods. Fas expression was flow cytometrically unimodal with heterogeneous density and showed quantitatively characteristic features among different diseases; weak in ALL, faint in CLL, moderate in HCL, and strong in ML, respectively. Not only full-length but also alternatively spliced truncated mRNAs were detected even in leukemic B-cells with qualitatively faint or negative Fas, and then band density of the former transcripts by RT-PCR was correlated to the Fas protein expression level. Short-term culture of freshly isolated cells gave rise to increases of Fas density and susceptibility for apoptosis, suggesting that the mRNA and inducible Fas are functional at least in vitro. These results show that Fas is a biological marker for characterizing B-cell neoplasms reflecting various stages of B-cell ontogeny and may have clinical utility as a therapeutic strategy.
- Published
- 1999
- Full Text
- View/download PDF
21. Heterogeneity of the inhibitory effects of IL-4 in two novel B lineage acute lymphoblastic leukemia cell lines.
- Author
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Renard N, Harada N, Callet-Bauchu E, Miyajima A, Duvert V, Banchereau J, and Saeland S
- Subjects
- Adult, Aged, Burkitt Lymphoma metabolism, Cell Division drug effects, Cell Survival drug effects, DNA Replication drug effects, DNA, Neoplasm biosynthesis, DNA, Neoplasm drug effects, Female, Humans, Male, Neoplasm Proteins metabolism, Phenotype, Phosphorylation drug effects, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-fes, Tumor Cells, Cultured drug effects, Burkitt Lymphoma drug therapy, Burkitt Lymphoma pathology, Interleukin-4 pharmacology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Protein-Tyrosine Kinases
- Abstract
The present study describes two novel cell lines, DUNATIS and SILVANUS, established from B lineage acute lymphoblastic leukemia patients. Respectively, DUNATIS and SILVANUS display an early pre-B cell and a pre-B cell phenotype. Spontaneous DNA replication of both cell lines was strongly inhibited by IL-4. This effect was directly mediated by IL-4 and exerted through the CD124 IL-4 receptor chain. Notably, IL-4 was associated with rapid cell death and reduction of cellularity in DUNATIS, whereas these parameters were considerably less pronounced and only observed after longer-term exposure of the SILVANUS cells to IL-4. In addition to these differences, although both cell lines expressed FES oncoprotein, a 100 kDa protein associated with FES was strikingly found to be tyrosine-phosphorylated in response to IL-4 exclusively in DUNATIS cells. These data demonstrate that IL-4 displays heterogenous effects on leukemic B cell precursors responsive to inhibition of DNA synthesis via IL-4 mediated engagement of the CD124 receptor chain. The present findings may be of use for appreciation of the effects of IL-4 in B lineage ALL, and the novel cell lines could represent a model for further identification of target molecules in IL-4 signalling.
- Published
- 1997
- Full Text
- View/download PDF
22. Differential phosphorylation of lamin B2 in normal and leukemic cells.
- Author
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Meier R, Müller PR, Hirt A, Leibundgut K, Ridolfi-Lüthy A, and Wagner HP
- Subjects
- Acute Disease, Antibodies, Monoclonal immunology, Bone Marrow pathology, Burkitt Lymphoma metabolism, Burkitt Lymphoma pathology, Cell Cycle, Humans, Lamins, Leukemia pathology, Leukemia, Myeloid metabolism, Leukemia, Myeloid pathology, Neoplasm Proteins immunology, Nuclear Proteins immunology, Peptide Mapping, Phosphoproteins immunology, Phosphorylation, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Tumor Cells, Cultured, Lamin Type B, Leukemia metabolism, Neoplasm Proteins metabolism, Nuclear Proteins metabolism, Phosphoproteins metabolism, Protein Processing, Post-Translational
- Abstract
Lamins constitute the nuclear lamina, which underlie the inner membrane of the cell nucleus. Phosphorylation of lamins is a key factor in the regulation of nuclear structure during the cell cycle and of gene transcription. Since an uncontrolled cell cycle and altered gene transcription are major characteristics of neoplasms, we looked for differences in lamin B2 phosphorylation between PBMC, ALL and AML cells. Using different lamin B2-specific antibodies, we detected two different lamin B2 species termed lamin B2 and B2A. Although phosphorylation of lamin B2 in leukemic cells was reminiscent of resting cells, the majority of ALL and AML samples showed significantly higher and more altered lamin B2A phosphorylation compared to PBMC. It remains to be elucidated which mechanism leads to these alterations and whether it could explain the extended G1-phase frequently observed in ALL cells.
- Published
- 1997
- Full Text
- View/download PDF
23. Beta 2-microglobulin and calnexin can independently promote folding and disulfide bond formation in class I histocompatibility proteins.
- Author
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Tector M, Zhang Q, and Salter RD
- Subjects
- Burkitt Lymphoma chemistry, Burkitt Lymphoma immunology, Burkitt Lymphoma metabolism, Calcium-Binding Proteins metabolism, Calnexin, Calreticulin, Cell Cycle immunology, Histocompatibility Antigens Class I biosynthesis, Humans, Oxidation-Reduction, Peptides chemistry, Peptides metabolism, Ribonucleoproteins metabolism, Tumor Cells, Cultured, Calcium-Binding Proteins physiology, Disulfides metabolism, Histocompatibility Antigens Class I chemistry, Histocompatibility Antigens Class I metabolism, Molecular Chaperones physiology, Protein Folding, beta 2-Microglobulin physiology
- Abstract
Class I histocompatibility proteins fold and assemble with beta 2-microglobulin (beta 2m) into heterodimers before binding short peptides in the endoplasmic reticulum. Here, we show that class I proteins rapidly form disulfide bonds, and that the process is highly reversible in Daudi cells lacking beta 2m. Three distinct class I protein conformations are present in equal amounts in these cells, each associated with the molecular chaperone calnexin. When binding of calnexin is inhibited by the glucosidase inhibitor castanospermine, fully oxidized class I proteins are no longer detected, suggesting that calnexin is required for completion of folding. However, in Daudi cells transfected to express beta 2m, castanospermine decreases only slightly the levels of fully oxidized class I proteins, indicating that folding is much less dependent on calnexin in the presence of beta 2m. Furthermore, calreticulin, a chaperone with functional similarities to calnexin, associates with class I molecules in beta 2m-positive cells. but not in Daudi cells, consistent with completion of folding and disulfide bond formation of class I heavy chains before binding to calreticulin occurs. This study demonstrates that calnexin and beta 2m can function independently to promote folding of class I heavy chains prior to formation of stable class I dimers.
- Published
- 1997
- Full Text
- View/download PDF
24. Promotion of IL8, IL10, TNF alpha and TNF beta production by EBV infection.
- Author
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Klein SC, Kube D, Abts H, Diehl V, and Tesch H
- Subjects
- Burkitt Lymphoma virology, Cytokines biosynthesis, Herpesviridae Infections metabolism, Humans, Interleukin-10 biosynthesis, Interleukin-8 biosynthesis, Tumor Cells, Cultured, Tumor Virus Infections metabolism, Burkitt Lymphoma metabolism, Herpesvirus 4, Human, Interleukins biosynthesis, Lymphotoxin-alpha biosynthesis, Tumor Necrosis Factor-alpha biosynthesis
- Abstract
Burkitt's lymphoma (BL) represents a high malignant B cell tumour. It has been proposed that cytokines are responsible for some of the characteristics of BL. We have analysed a panel of different BL and lymphoblastoid cell lines (LCLs) for the expression of cytokines, including: IL 1 alpha, IL 1 beta, IL2, IL3, IL4, IL6, IL8, IL10, TNF alpha and TNF beta and for the soluble cytokine receptor for IL2 (slL2R). Our results show that expression of IL8, IL10, TNF alpha or TNF beta was detected frequently in several of the Burkitt or lymphoblastoid cell lines. There was a correlation between Epstein-Barr virus (EBV) infection and cytokine protein production. Our results suggest that EBV promote the expression of IL8, IL10, TNF alpha and TNF beta.
- Published
- 1996
- Full Text
- View/download PDF
25. Differential effect of heat shock on RNA metabolism in human Burkitt's lymphoma B-cell lines.
- Author
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Kumar A, Kurl RN, Kryworuchko M, Diaz-Mitoma F, and Sharma S
- Subjects
- Burkitt Lymphoma enzymology, Burkitt Lymphoma virology, Cell Transformation, Viral, Endonucleases metabolism, Gene Expression, Genes, myc, HSP70 Heat-Shock Proteins genetics, Herpesvirus 4, Human, Humans, Polynucleotide Adenylyltransferase metabolism, RNA, Messenger metabolism, Burkitt Lymphoma metabolism, Hot Temperature, RNA, Neoplasm metabolism
- Abstract
Thermal stress induces expression of a family of heat shock proteins which may regulate the synthesis of various cellular genes. We investigated the effect of heat shock on polyadenylation in Epstein-Barr Virus (EBV) negative and EBV transformed human Burkitt's lymphoma (BL) B-cell lines. Incubation of the BL B-cell line P3HR-1, carrying the defective EBV genome [EBV nuclear antigen-2 gene deletion] at 46 degrees C for 15 min increased nuclear poly(A) polymerase (PAP) activity. Thereafter, enzymatic activity declined and at 60 min it was reduced to about 50% of that observed in cells incubated at 37 degrees C. In contrast, no significant increase in PAP activity was observed at 15 min or thereafter in an EBV- BL cell line, ST-486, in response to elevated temperature. Furthermore, no heat shock mediated change in nuclear poly(A)-specific endonuclease activity was observed in either P3HR-1 or ST-486 cells suggesting a specific effect on PAP activity. However, thermal stress dependent increase in c-myc expression was detected only in P3HR-I cells. These results suggest an association between EBV transformation and enhanced expression of c-myc and PAP activity. To further determine the role of EBV, and EBV- BL cell line, BL-30, and BL-30 cells infected in vitro with a wild type strain of EBV, BL-30/B95-8, were investigated. BL-30/B-95-8, unlike the parental BL-30 cells, exhibited c-myc and PAP gene upregulation at 15 min but were downregulated at 60 min following exposure of cells to elevated temperatures. These results suggest that infection of human B-cells with EBV is associated with their ability to respond to thermal stress by increased PAP activity which may stabilize mRNA through enhanced polyadenylation.
- Published
- 1995
- Full Text
- View/download PDF
26. The protein kinase C inhibitor H7 blocks phosphorylation of stathmin during TPA-induced growth inhibition of human pre-B leukemia REH6 cells.
- Author
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Duraj J, Kovacikova M, Sedlak J, Koppel J, Sobel A, and Chorvath B
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Burkitt Lymphoma metabolism, Calmodulin antagonists & inhibitors, Cell Cycle drug effects, Cell Division drug effects, Humans, Imidazoles pharmacology, Phosphorylation, Preleukemia metabolism, Stathmin, Tumor Cells, Cultured, Burkitt Lymphoma pathology, Isoquinolines pharmacology, Microtubule Proteins, Phosphoproteins metabolism, Piperazines pharmacology, Preleukemia pathology, Protein Kinase C antagonists & inhibitors, Tetradecanoylphorbol Acetate pharmacology
- Abstract
The human pre-B acute lymphoblastic leukemia cell line REH6 was used to analyze the regulation of a ubiquitous intracellular phosphoprotein stathmin (Mr 19,000, pl = 5.6-6.2). We demonstrated by 32P-labeling that the short (1 h) treatment of the REH6 cells with the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), resulted in a rapid phosphorylation of at least three (P1, P2 and P3) stathmin isoforms without an alteration of stathmin isoform expression. Furthermore, Western blot analysis with specific antiserum showed that the prolonged period (48 h) of TPA treatment partially reduced protein levels particularly of two (N2 and P2) stathmin isoforms. The potent and relatively specific protein kinase C (PKC) inhibitor, 1,(5-isoquinolinesulphonyl)2methylpiperasine dihydrochloride (H7), partially inhibited these TPA effects, whereas the specific calmodulin inhibitor R24571 (calmidazolium) had no effect upon these events. Our findings suggest that stathmin phosphorylation in REH6 cells could be in part mediated by PKC activation.
- Published
- 1995
- Full Text
- View/download PDF
27. Exogenous expression of human granulocyte colony-stimulating factor receptor in a B-lineage acute lymphoblastic leukemia cell line: a possible model for mixed lineage leukemia.
- Author
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el-Sonbaty SS, Tsuchiya H, Watanabe M, Hochito K, Kunisada T, Shimosaka A, and Matsuda I
- Subjects
- Burkitt Lymphoma immunology, Burkitt Lymphoma pathology, Cell Division drug effects, Clone Cells, Granulocyte Colony-Stimulating Factor pharmacology, Humans, Immunophenotyping, In Vitro Techniques, Transfection, Tumor Cells, Cultured, Burkitt Lymphoma metabolism, Receptors, Granulocyte Colony-Stimulating Factor metabolism
- Abstract
We report evidence that the granulocyte colony-stimulating factor (G-CSF) receptor is present and may be functioning on blast cells from some patients with myeloid surface antigen positive (My+) acute lymphoblastic leukemia (ALL). In the present study, a human G-CSF receptor expression plasmid was transfected into a newly established B-lineage ALL cell line 'Tanoue' and its subclone 'ST' by lipofection to investigate whether expression of the G-CSF receptor and G-CSF stimulation would induce myeloid characteristics on myeloid surface antigen negative (My-) ALL cells. The G-CSF receptor became detectable on the transfected cells (GR-Tanoue and GR-ST), with dissociation constant values of 50-130 pmol/l, and maximal binding sites (Bmax of 77-6100 sites/cell on receptor binding assays. Short term culture with recombinant human G-CSF induced myeloid differentiation (a two to three-fold increase in CD33 and CD15 expression), and a moderate 3H-thymidine uptake (stimulation index, 1.75) only in the GR-ST clone no. 15 which expressed a high number of G-CSF receptors (Bmax, 6100 sites/cell). Our data show that (a) exogenous expression of the G-CSF receptor and G-CSF stimulation can induce myeloid characteristics on ALL cells; and (b) in the G-CSF receptor-expressing cells, there is a correlation between the number of G-CSF receptors and cell responsiveness to G-CSF in either proliferation or differentiation.
- Published
- 1995
- Full Text
- View/download PDF
28. Constitutive production of interleukin-8 (IL-8) by normal and malignant human B-cells and other cell types.
- Author
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Srivastava MD, Srivastava R, and Srivastava BI
- Subjects
- Blotting, Southern, Burkitt Lymphoma metabolism, Cell Line, DNA Probes, Enzyme-Linked Immunosorbent Assay, HTLV-I Infections metabolism, HTLV-II Infections metabolism, Humans, Interleukin-8 analysis, Reference Values, B-Lymphocytes metabolism, Interleukin-8 biosynthesis, Leukemia metabolism, T-Lymphocytes metabolism, Tumor Cells, Cultured metabolism
- Abstract
The culture supernatants from 43 human cell lines obtained during log phase and from purified normal peripheral blood B-lymphocytes cultured at 10(6) cells ml-1 for 48 h in RPMI 1640-5% fetal calf serum were examined for interleukin-8 (IL-8) using Elisa kits. Constitutive IL-8 production was found for 14/15 B-cell lines (5 derived from normal persons and 2 from AML patients, 1 pre-B-ALL, 2 CLL with trisomy 12, 2 HTLV-I+, 1 HTLV-II+, 1/2 Burkitt lymphoma), 4/16 T-cell lines (3/6 HTLV-I+, 1 HTLV-II+, 0/9 T-ALL), myeloid line HL-60, monocytoid line U937, 3/3 ovarian carcinoma, 1/1 endometriosis, 2/2 normal fibroblast, 0/2 C-ALL, 0/1 pre-erythroid line K562, as well as for normal B-lymphocytes. Later, cells examined by indirect immunofluorescence using IL-8 antibodies gave a positive reaction. DNA from 4 IL-8 producing and 3 non-producing cell lines, when probed with IL-8 cDNA gave the same 3.5 kb EcoRI fragment indicating similarities of the IL-8 gene in these cells. Two B-cell lines examined showed the expression of 1.8 kb IL-8 mRNA. These results indicate IL-8 production by a greater variety of cells than previously believed which open possibilities for new IL-8-mediated immune functions by such cells as B-cells.
- Published
- 1993
- Full Text
- View/download PDF
29. Expression of p53 in human leukemic cell lines.
- Author
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Kraiss S, Espig R, Vetter U, Hartmann W, and Montenarh M
- Subjects
- Burkitt Lymphoma immunology, Burkitt Lymphoma pathology, Electrophoresis, Polyacrylamide Gel, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Molecular Weight, Polymers, Precipitin Tests, Protein Conformation, Tumor Cells, Cultured immunology, Tumor Cells, Cultured metabolism, Tumor Suppressor Protein p53 immunology, Burkitt Lymphoma metabolism, Leukemia, Myeloid, Acute metabolism, Tumor Suppressor Protein p53 metabolism
- Abstract
The cell-encoded p53 antigen seems to be tightly associated with various human malignancies. We have analyzed biochemical properties of p53 in two different cell lines derived from patients with ALL or ANLL. p53 was found in elevated levels in both leukemic cell lines compared to unstimulated or stimulated normal lymphocytes. High levels of p53 in these cell lines are due to an extended stability of p53 protein rather than to different rates of synthesis. p53 from both cell lines formed low- and high-molecular weight oligomers which revealed that p53 exists in a heterogenous population in these tumor cells. The presence of immunologically different subsets of p53 was demonstrated by sequential immunoprecipitation experiments with different p53 specific monoclonal antibodies. Our results showed structural and immunological variabilities of p53 in cell lines derived from human tumors and may thus provide an insight into the role p53 may play in human malignancies.
- Published
- 1990
- Full Text
- View/download PDF
30. A comparison of established human lymphoma lines by flow cytometry: quantitation of Ricinus communis agglutinin binding and the effect of specific glycosidases.
- Author
-
Brossmer R, Bohn B, Sauer A, and zur Hausen H
- Subjects
- Binding Sites, Cell Line, Cell Transformation, Viral, Flow Cytometry, Herpesvirus 4, Human, Humans, Plant Lectins, Burkitt Lymphoma metabolism, Ricinus communis, Galactosidases pharmacology, Lectins metabolism, Neuraminidase pharmacology, Plants, Toxic, Ricinus, beta-Galactosidase pharmacology
- Abstract
Two established cell lines of human B-cell lymphomas derived from Burkitt lymphomas and their Epstein-Barr virus-transformed counterparts were analyzed with respect to their ability to bind the beta-galactoside-specific lectin Ricinus communis agglutinin (RCA). Native and sialidase- as well as sialidase-beta-galactosidase-treated cells were compared. The method for the quantitative determination of average numbers of binding sites and of apparent affinity constants was flow cytometry with fluorescence-labeled lectin. Although with native cells there was no significant deviation of the values for virus-transformed cells from those for the parent cells, some differences could be detected after glycosidase treatment. The general procedure of the combined application of specific glycosidases and the quantitation of sugar-specific lectin binding is recommended as a general strategy for the differentiation of cells with known or putative differences in biological functions.
- Published
- 1985
- Full Text
- View/download PDF
31. Prediction of sensitivity to 1-beta-D-arabinofuranosylcytosine by the plateau level of its 5'-triphosphate in human lymphoblastic cell lines in vitro.
- Author
-
Abe I, Saito S, Hori K, Suzuki M, and Sato H
- Subjects
- Burkitt Lymphoma metabolism, Cell Line, Cytarabine therapeutic use, DNA biosynthesis, Humans, Leukemia, Lymphoid drug therapy, Arabinofuranosylcytosine Triphosphate metabolism, Arabinonucleotides metabolism, Cytarabine metabolism, Leukemia, Lymphoid metabolism
- Abstract
Parameters for metabolism of 1-beta-D-arabinofuranosylcytosine (ara-C) were examined to know whether the prediction of ara-C sensitivity is possible or not using 9 human lymphoblastic cell lines, 3 T cell lines and 6 B cell lines in vitro. Neither the capacity for synthesis, degradation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP), generally lower in the T than B cell lines, nor deamination of ara-C, negligible in the B cell lines, could be correlated to the drug sensitivity. On the other hand, significant correlation was obtained between the sensitivity and the plateau level of ara-CTP. We consider that ara-C sensitivity could be predicted by measuring the plateau ara-CTP level before commencement of chemotherapy.
- Published
- 1983
- Full Text
- View/download PDF
32. Comparison of membrane proteins of Burkitt's lymphoma and EBV-transformed B lymphoblast cell lines and of Con A-activated T lymphocytes and T lymphoblast cell lines.
- Author
-
Spiro RC, DeMartino JL, Boto W, Lazarus H, and Humphreys RE
- Subjects
- Cell Differentiation, Cell Line, Concanavalin A pharmacology, Herpesvirus 4, Human, Humans, Lymphocyte Activation, Molecular Weight, B-Lymphocytes metabolism, Burkitt Lymphoma metabolism, Cell Transformation, Neoplastic, Membrane Proteins metabolism, Neoplasm Proteins metabolism, T-Lymphocytes metabolism
- Published
- 1979
- Full Text
- View/download PDF
33. Protein A vectorized toxins--II. Preparation and "in vitro" cytotoxic effect of protein A-ricin A chain conjugate on antibody coated human tumour cells.
- Author
-
Ghetie MA, Moraru I, Margineanu M, and Ghetie V
- Subjects
- Burkitt Lymphoma metabolism, Cell Survival, Chromatography, Affinity, Humans, Staphylococcal Protein A metabolism, Tumor Cells, Cultured, Burkitt Lymphoma pathology, Immunoglobulin G immunology, Ricin pharmacology, Staphylococcal Protein A pharmacology
- Abstract
Protein A of Staphylococcus aureus was covalently bound to reduced ricin A chain toxin by N-succinimidyl 3-(2-pyridyldithio)propionate. The conjugate consisting mainly of one molecule of protein A bound to two molecules of A chains (Mr 107,000) was purified by tandem affinity chromatography on ConA-Sepharose 4B and IgG-Sepharose 4B. The purified protein A-A chain conjugate was able to bind and kill human lymphoma cells coated either with monoclonal mouse IgG2a anti-kappa antibody or with polyclonal rabbit anti-kappa antibody. The cytotoxic activity of protein A-A chain conjugate in conjunction with either mouse or rabbit anti-kappa antibodies was 10 times higher than that of rabbit IgG anti-mouse IgG coupled with A chain on Daudi cells coated with mouse anti-kappa antibody and 100 times higher than that of rabbit anti-kappa antibody coupled with A chain on non-coated Daudi cells. The cytotoxic effect of protein A-A chain conjugate on antibody-coated Daudi cells (9 x 10(-12) M) was comparable with that of ricin toxin on non-coated Daudi cells (2 x 10(-12) M). The results recommend the use of protein A-ricin A chain toxin conjugate as a unique specific toxin for the "in vitro" killing of antibody-coated target cells.
- Published
- 1988
- Full Text
- View/download PDF
34. The DNA synthesis of leukemic (L2C) guinea pig B lymphocytes involves a permanent activation of protein kinase C without corresponding phosphoinositide hydrolysis.
- Author
-
Vial HJ, Parant MR, Marie JS, Laurent AM, and Le Peuch CJ
- Subjects
- Animals, B-Lymphocytes enzymology, Burkitt Lymphoma enzymology, Burkitt Lymphoma genetics, Cell Line, Chromatography, DEAE-Cellulose, Cyclic AMP antagonists & inhibitors, Enzyme Activation, Female, Guinea Pigs, Hydrolysis, Phosphatidic Acids biosynthesis, Phosphatidylinositol 4,5-Diphosphate, Phosphatidylinositols biosynthesis, Phospholipids analysis, Protein Kinase C antagonists & inhibitors, Tumor Cells, Cultured enzymology, Tumor Cells, Cultured metabolism, B-Lymphocytes metabolism, Burkitt Lymphoma metabolism, DNA biosynthesis, Phosphatidylinositols metabolism, Protein Kinase C metabolism
- Abstract
L2C B lymphocytes have a constant high DNA synthesis due to their continuous proliferative state. The addition of polymyxin B (PmB), a rather selective inhibitor of protein kinase C, stopped (3H)thymidine incorporation with an IC50 of 10 microM when added 18 h before measuring DNA synthesis. Interestingly, PmB inhibition of DNA synthesis was suppressed when 4 nM 12-O-tetradecanoylphorbol-13-acetate was added along with PmB, indicating that PmB may act through inhibition of protein kinase C. In the node and spleen lymphocytes of normal guinea pigs, protein kinase C activity was entirely cytosolic and was eluted at 0.12 M NaCl when adsorbed on DEAE-cellulose. In L2C leukemic lymphocytes, total protein kinase C activity was of the same order of magnitude, but 20% of it was associated with the membrane fraction. The lipid-dependent activity, eluted at 0.12 M NaCl from cytosolic and membrane fractions, was suppressed by staurosporine with an IC50 of 10-40 nM and by polymyxin B with an IC50 of 2-6 microM. Phosphoinositide metabolism was studied in the transformed cells. Incorporation of 32Pi into polyphosphoinositides was considerable, whereas much more time was required for a tiny incorporation of inositol. We detected no release of radioactive inositol triphosphate. Taken together, these results suggest that protein kinase C function is indispensible for triggering L2C leukemic lymphocyte proliferation. The causes of this permanent activation merit further investigation.
- Published
- 1989
- Full Text
- View/download PDF
35. 7-Hydroxymethotrexate cytotoxicity and selectivity in a human Burkitt's lymphoma cell line versus human granulocytic progenitor cells: rescue by folinic acid and nucleosides.
- Author
-
Fabre I, Fabre G, and Cano JP
- Subjects
- Cell Line, Colony-Forming Units Assay, Granulocytes drug effects, Humans, Leucovorin pharmacology, Methotrexate pharmacology, Burkitt Lymphoma metabolism, Folic Acid Antagonists pharmacology, Hematopoietic Stem Cells drug effects, Methotrexate analogs & derivatives
- Abstract
The cytotoxicity of 7-hydroxymethotrexate (7-OH-MTX), the primary plasma metabolite of methotrexate (MTX) in humans, was assessed by inhibition of colony formation in agar, using human bone marrow granulocyte-macrophage stem cells (CFU) from healthy volunteers and RAJI cells, a human Burkitt's lymphoma cell line. After a 2 hr exposure of cells to 7-OH-MTX, the concentrations necessary to produce a 50% inhibition of colony formation were 180 microM and 10 microM for bone marrow cells and for RAJI cells respectively. A continuous incubation with 20 microM folinic acid (CF) protected the RAJI cells from 7-OH-MTX cytotoxicity at concentrations below 5 microM but was not able to completely reverse 7-OH-MTX effects at higher doses. Continuous incubation of 7-OH-MTX-preloaded cells (2 hr, ID90) with the end products of folate-dependent reactions, adenosine (100 microM) and thymidine (10 microM), completely rescued RAJI cells from the 7-OH-MTX cytotoxic effects. Moreover, while thymidine alone had no effect on the 7-OH-MTX response curve, both adenosine alone or CF-adenosine combination produced 75% and 90% protection respectively. CF and adenosine concentrations necessary to achieve 90% protection were 20 and 100 microM respectively. This study demonstrates that 7-OH-MTX can exhibit a cytotoxic selectivity for this human Burkitt's lymphoma cell line as compared to human bone marrow stem cells and the cytotoxicity of 7-OH-MTX cannot be reversed by CF alone. These data suggest that 7-OH-MTX and/or its polyglutamylated derivatives may play an important role on different enzyme(s) involved in the interconversion of tetrahydrofolate cofactors necessary for the de novo purine biosynthesis.
- Published
- 1986
- Full Text
- View/download PDF
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