| 1. |
- Jerkeman, Mats, et al.
(författare)
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Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma-a Nordic Lymphoma Group study.
- 2004
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Ingår i: Annals of Hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 83:7, s. 414-419
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.
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| 2. |
- Storlazzi, CT, et al.
(författare)
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A novel chromosomal translocation t(3;7)(q26;q21) in myeloid leukemia resulting in overexpression of EVI1
- 2004
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Ingår i: Annals of Hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 83:2, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- The EVI1 proto-oncogene encodes a nuclear zinc finger protein that acts as a transcription repressor factor. In myeloid leukemia it is often activated by chromosomal rearrangements involving band 3q26, where the gene has been mapped. Here we report two leukemia cases [a chronic myeloid leukemia blast crisis (CML-BC) and an acute myeloid leukemia (AML) M4] showing a t(3;7)(q26;q21) translocation in a balanced and unbalanced form, respectively. Fluorescent in situ hybridization (FISH) analysis revealed that both patients showed a breakpoint on chromosome 3 inside the clone RP11-33A1 containing the EVI1 oncogene and, on chromosome 7, inside the clone RP11-322M5, partially containing the CDK6 oncogene which is a D cyclin-dependent kinase gene, observed to be overexpressed and disrupted in many hematological malignancies. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed overexpression of EVI1 in both cases, but excluded the presence of any CDK6/EVI1 fusion transcript. CDK6 expression was also detected. Together, these data indicate that EVI1 activation is likely due not to the generation of a novel fusion gene with CDK6 but to a position effect dysregulating its transcriptional pattern.
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| 3. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura.
- 2000
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Ingår i: Annals of hematology. - 0939-5555. ; 79:9, s. 507-13
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Tidskriftsartikel (refereegranskat)abstract
- Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-beta1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) < 50 x 10(9)/l, (2) 50-150 x 10(9)/l and (3) > 150 x 10(9)/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-beta1 in patients with pltc >150x10(9)/l (23.5+/-2.8ng/ml), compared with patients with pltc <50x10(9)/l (2.3+/-0.6 ng/ml; P<0.0001), patients with pltc 50-150x 10(9)/l (7.2+/-1.7 ng/ml; P<0.0001) and healthy volunteers (9.8+/-1.3 ng/ml; P<0.01). The serum levels of the Thl cytokines interleukin (IL)-2 and interferon (IFN)-y were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50 x 10(9)/l had significantly lower levels (0.6+/-0.1 pg/ml) than both patients with pltc 50-150 x 10(9)/l (1.8 +/- 0.1 pg/ml; P<0.005) and healthy volunteers (1.4+/-0.1 pg/ml; P<0.005). Furthermore, patients with pltc <50 x 10(9)/l and splenectomised patients had significantly higher levels of CD4 + CD25 + activated T cells [26.2 +/- 14.8% (P<0.05) and 26.7+/-11.9% (P<0.005), respectively] than healthy controls (16.5+/-4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150 x 10(9)/l were significantly elevated (26.6+/-16.0%; P<0.05) compared with controls (17.4+/-7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-beta1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-beta1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease.
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| 4. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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Leukemic transformation of essential thrombocythemia without previous cytoreductive treatment.
- 2000
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Ingår i: Annals of hematology. - 0939-5555. ; 79:1, s. 40-2
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Tidskriftsartikel (refereegranskat)abstract
- Blastic transformation of essential thrombocythemia (ET) preceded by chemotherapy is occasionally described in the literature. In ET as well as in other myeloproliferative disorders the leukemogenic effect of alkylating agents and (32)P is well established, and recent reports also indicate a certain leukemogenic effect of hydroxyurea in these disorders. However, leukemic transformation in untreated ET seems to be a rare event. This is probably due to the fact that, at some time during their clinical course, most ET patients receive chemotherapy and are thereby exposed to leukemogenic challenge. We report on a woman with ET who had not received cytoreductive treatment prior to the development of acute myeloid leukemia, indicating that this transformation was a natural progression of her disorder.
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