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

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.
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PMID:Expression patterns of costimulatory molecules on cells derived from human hematological malignancies. 989 58

We have studied 215 male patients (aged 45-97 years) whose sole cytogenetic abnormality was clonal loss of the Y chromosome in metaphase cells from unstimulated cultures. The patients comprised a control group with no evidence of hematologic disease and four disease case groups: 1) myelodysplastic syndrome (MDS), refractory anemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia; 2) acute myelogenous leukemia; 3) myeloproliferative disorder (MPD), chronic granulocytic leukemia, and polycythemia vera; and 4) B-cell lymphoma/leukemia. The frequency of cells with Y loss increased with age and was significantly greater in cases than in controls, but it was not correlated with survival or with prior therapy. The frequency of cases with a -Y clone was 6.3% of male karyotypes and represented 16.4% of all abnormal male cytogenetic reports. Much of the difference between cases and controls appears to be accounted for by a greater frequency of cases with > 75% Y loss. A value of 81% chromosome Y loss maximized the combined sensitivity (28%) and specificity (100%) for predicting disease status, but a 75% cutoff provided the best estimate of disease risk. Even in older males, if > 75% of metaphase cells are 45,X,-Y, they probably represent a disease-associated clonal population, and it is possible that the critical genetic change is not visible through the microscope. This observation is true for MDS, MPD, B-cell disease, and especially acute myelogenous leukemia. The prognostic association of Y chromosome loss for survival appears to be neutral or favorable. Genes Chromosomes Cancer 27:11-16, 2000.
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PMID:Clinical significance of Y chromosome loss in hematologic disease. 1056 81

Myelodysplastic syndromes (MDS) are characterized by dyserythropoiesis resulting in anemia. This pathological hallmark is incompletely understood. Notch signaling has been linked to impaired erythropoietic and megakaryopoietic development of CD34+ progenitor cells, but its role in MDS is unclear. We have analyzed the transcriptional activity of Notch pathway elements and its association with the key erythroid factor globin transcription factor 1 (GATA1) and the apoptosis regulatory gene B-cell lymphoma-xl (BCLxl) in MDS. The methylation of GATA1 erythroid promoter CpG dinucleotides flanking cis-regulatory elements, including an N-box suppressor binding site for HES1 and a GATA-box binding site, was examined in normal and MDS erythropoiesis. We have generated a kinetic in vitro model of MDS erythropoiesis using CD34+ bone marrow cells from healthy donors (n = 7) and patients with MDS (low risk: RA/n = 6, RARS/n = 3; high risk: RAEB/n = 4, RAEB-T/n = 2). RNA expression of GATA1, BCLxl, DLK1, Notch1, HES1, and HERP2 was measured by real-time RT-PCR (qPCR). DNA methylation at seven CpG dinucleotides of the GATA1 gene promoter was quantitatively analyzed by pyrosequencing of bisulfite-treated genomic DNA at any specific time point. For the Notch pathway elements, no conclusive expression differences were found between MDS and normal erythropoiesis. But we found steadily up-regulated RNA expression of GATA1 and of BCLxl during late normal erythropoietic differentiation. In contrast, during MDS, erythropoiesis a loss of typical up-regulation of GATA1 and BCLxl was observed. Hypermethylation of CpG dinucleotides flanking the repressor HES1 binding site within the 5' region of GATA1 was detected particularly during late MDS erythropoiesis. Interestingly, decremental GATA1 promotor methylation values were seen during normal erythropoiesis matching GATA1 RNA up-regulation. Our data show that the critical erythropoietic transcription factor GATA1 as well as the antiapoptotic molecule BCLxl fails to be normally up-regulated during MDS erythropoiesis. The higher residual 5'-GATA1 methylation values in MDS erythropoiesis but decremental loss thereof in normal erythropoiesis suggest a gene dose effect for GATA1 during erythropoiesis being finely tuned by CpG methylation. Its dysregulation may contribute to the ineffective erythropoiesis observed in MDS.
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PMID:Epigenetic dysregulation of GATA1 is involved in myelodysplastic syndromes dyserythropoiesis. 2196 5