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 following report is of a case of diffuse B-cell lymphoma of the anterior mediastinum that was originally treated by resection and radiation in a patient who had pleural and subcutaneous metastases four months after operation. A total dose of 120 mg of CDDP, 60 mg of BLM, and 15 mg of VBL was administered in five weeks. The metastases completely disappeared by this dose alone, and the patient is alive and well seven and a half years after the chemotherapy.
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PMID:[Diffuse B-cell lymphoma of anterior mediastinum cured by short-term administration of CDDP-containing regimen]. 246 28

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted growth infertility and immunodeficiency. In addition, BS patients are highly predisposed to cancers. Although recently the causative gene of BS (BLM) was identified as a DNA helicase homologue, the function of BLM in DNA replication has not been elucidated. In this study, p53 mutation and microsatellite instability in B-cell lymphomas originating from 2 sibling BS patients were investigated. In the originally developed tumor of both patients, no p53 mutation was detected. In one patient, however, after treatment by ionizing radiation the B-cell lymphoma recurred, showing a 9-bp deletion in exon 7. In lymphoma cells and an EB-virus-transformed cell line from BS lymphocytes of this patient, microsatellite instability was also detected from the reduced length of microsatellite DNA markers, although in the other patient microsatellite instability was not detected. Thus, 2 B-cell lymphomas, despite having the same BLM mutation, showed different phenotypes in terms of p53 mutation and microsatellite instability.
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PMID:Microsatellite instability in B-cell lymphoma originating from Bloom syndrome. 898 Feb 51

Donor-cell leukemia post bone marrow transplantation is a rare event. Most of the cases reported to date have developed in cells from an HLA-matched sibling, who had no evidence of malignant disease before or following the occurrence of donor-origin leukemia. We describe a 17-year-old female who developed B-cell lymphoma 9 years following the occurrence of donor-origin acute myeloid leukemia in her brother for whom she had donated marrow. Cytogenetic analysis of the tumor revealed multiple chromosomal aberrations. The donor was heterozygous for the Ashkenazi mutation of Bloom's syndrome, suggesting that donor-type leukemia could have resulted from genomic instability in the donor cells.
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PMID:B-cell lymphoma developing in the donor 9 years after donor-origin acute myeloid leukemia post bone marrow transplantation. 1274 72

The article highlighted in this issue is "Reversal of Bcl-2 Mediated Resistance of the EW36 Human B-Cell Lymphoma Cell Line to Arsenite and Pesticide-Induced Apoptosis by PK11195, a Ligand of the Mitochondrial Benzodiazepine Receptor" by Donna E. Muscarella, Kerry A. O'Brien, Ann T. Lemley, and Stephen E Bloom from Cornell University in Ithaca, NY (pp. 66-73). The following brief review summarizes their findings, highlights the novel biological model and experimental approach used, and explores potential mechanistic and therapeutic implications of these findings.
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PMID:The mitochondrial benzodiazepine receptor as a potential target protein for drug development: demonstration of functional significance with cell lines exhibiting differential expression of Bcl-2. 1273 Jun 27

The RecQ family helicase BLM is critically involved in the maintenance of genomic stability, and BLM mutation causes the heritable disorder Bloom's syndrome. Affected individuals suffer from a predisposition to a multitude of cancer types and an ill-defined immunodeficiency involving low serum Ab titers. To investigate its role in B cell biology, we inactivated murine Blm specifically in B lymphocytes in vivo. Numbers of developing B lymphoid cells in the bone marrow and mature B cells in the periphery were drastically reduced upon Blm inactivation. Of the major peripheral B cell subsets, B1a cells were most prominently affected. In the sera of Blm-deficient naive mice, concentrations of all Ig isotypes were low, particularly IgG3. Specific IgG Ab responses upon immunization were poor and mutant B cells exhibited a generally reduced Ab class switch capacity in vitro. We did not find evidence for a crucial role of Blm in the mechanism of class switch recombination. However, a modest shift toward microhomology-mediated switch junction formation was observed in Blm-deficient B cells. Finally, a cohort of p53-deficient, conditional Blm knockout mice revealed an increased propensity for B cell lymphoma development. Impaired cell cycle progression and survival as well as high rates of chromosomal structural abnormalities in mutant B cell blasts were identified as the basis for the observed effects. Collectively, our data highlight the importance of BLM-dependent genome surveillance for B cell immunity by ensuring proper development and function of the various B cell subsets while counteracting lymphomagenesis.
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PMID:Genomic instability resulting from Blm deficiency compromises development, maintenance, and function of the B cell lineage. 1910 66

We have analyzed chromosome abnormalities in 32 B-cell lymphoma (B-ML), 29 T-cell lymphoma (T-ML) and 29 adult T-cell leukemia/lymphoma (ATL) patients and tested the reactivity of Bloom syndrome (BS) derived malignant lymphoma (ML) antigen with the sera in these patients with immunofluorescence (IF) and Western blotting (WB) protocols. Among the cases analyzed, 14q32 abnormalities were observed in 11 (B-ML), 8 (T-ML) and 10 (ATL) cases; these changes were accompanied by complex numerical and structural abnormalities. In the IF and WB analyses, the reactivity of BS ML antigen and ML sera showed high positivity in over 85% of ML cases and appeared to clearly raise the number of successful diagnoses as compared to the chromosome finding, giving 50-60% success in identifying ML. WB analyses demonstrated common ML antigen band at 97 KD (B-ML, T-ML and ATL). DNA analysis from BS ML antigen cells (BS-SHI-4M ML) showed rearranged fragments in both T-cell receptor (TCR alpha3 and immunoglobulin joining region (I(g)J(H) genes. The present findings of rearrangements of TCR alpha3 and I(g)J(H) in BS-SHI-4M ML antigen cells possibly support the common reactivity of BS ML antigen to B- and T-ML and ATL sera. The possible role of immunoglobulin heavy chain variable region (I(g)V(H) gene mutation and ML antigen expression is discussed.
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PMID:Interaction of bloom-syndrome cellular cancer antigens with sera of malignant-lymphoma patients - an immunological and cytogenetical study. 2156 55

This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. This case highlights that the rituximab-based chemotherapy protocol is an effective and safe treatment alternative for mature B-cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment.
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PMID:Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome. 2796 5

We report the case of a young woman who developed, 3 years after stopping Rituximab (RTX) prescribed for immune thrombocytopenia (ITP), a severe immunodeficiency leading to fatal pulmonary Epstein-Barr virus-positive diffuse large B-cell lymphoma. Genetic analysis led us to identify four missense mutations known to affect immune-deficiency-associated genes (FAS-ligand (FASL) gene (p.G167R); perforin-1 (PRF1 (p.R55C) gene; the Bloom syndrome RecQ-Like helicase (BLM) gene and the Moesin (MSN) (p.A122T) gene). The heterozygous mutation in the FASL gene, not present in the Genome Aggregation Database or ClinVar database, could suggest atypical Autoimmune LymphoProliferative Syndrome and its role in this patient's immunodepression is discussed. This observation strengthens the role of FASL gene mutation in severe clinical phenotypes of primary immune deficiency and raises new questions about the genetic background of ITP occurring in young people in a context of immunodeficiency.
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PMID:Fatal Hypogammaglobulinemia 3 Years after Rituximab in a Patient with Immune Thrombocytopenia: An Underlying Genetic Predisposition? 3195 52

Pralatrexate (Folotyn; PLX) and belinostat (Beleodaq; BLS) are registered for the treatment of patients with peripheral T-cell lymphoma (PTCL) and are being considered for other lymphomas. In this study we investigated whether BLS had the ability to potentiate the cytotoxicity of PLX. A panel of lymphoma cell lines was used for the combination studies: the B-cell SUDHL-4, SUDHL-5, HT, Jeko-1 and T-cell Karpas-299 and Hut-78. Uptake of PLX was mediated by the reduced folate carrier (RFC). PLX showed a 6-fold better RFC substrate affinity compared to methotrexate, and 2-fold better than levoleucovorin (l-LV). Sensitivity expressed as the concentration that resulted in 50% growth inhibition (IC50) after 72 hr exposure to PLX varied from 2.8 to 20 nM and for BLS from 72 to 233 nM, independent of the background of the cell lines. The interaction between BLS and PLX was studied using the median-drug effect analysis. At a fixed molar ratio between the drugs based on the IC50 concentration the average combination index (CI) for all cell lines showed additivity (CI: around 1.0). In three selected cell lines (SUDHL-4, SUDHL-5, and HT) sequential exposure (24 h pretreatment with BLS, followed by 48 h to PLX + BLS), did not improve interaction (CI: 0.9-1.4). As an alternative approach a non-fixed ratio was used by exposing SUDHL-4, SUDHL-5, and HT cells to IC25 concentrations of either BLS or PLX in combination with the other drug. Exposure to IC25 of PLX did not decrease the IC50 for BLS (CI from 0.6-1.2), but exposure to IC25 of BLS markedly increased PLX sensitivity (low CIs from 0.40 to 0.66). Mechanistic studies focused on induction of apoptosis, and showed cleavage of predominantly caspase-9 in HT and SUDHL-4 cells for both drugs at their IC50s, being similar in the combination setting. Moreover, at these concentrations, the drugs were shown to confer an S-phase arrest. In conclusion, the combination of PLX and BLS showed additivity in various lymphoma cell lines, with a schedule-dependent synergism in B-cell lymphoma. Based on these data, proficient inhibition of HDAC activity by BLS holds promise in sensitization of tumor cells to PLX.
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PMID:Schedule-Dependent Synergy Between the Histone Deacetylase Inhibitor Belinostat and the Dihydrofolate Reductase Inhibitor Pralatrexate in T-and B-cell Lymphoma Cells in vitro. 3316 92