Posted by rob on October 30, 2005 under Uncategorized |
Koca E, Cetiner D, Goker H, Aksu S, Ozcebe OI, Haznedaroglu IC, Turgan C
Clin Nephrol. 2005 Oct ; 64(4): 324-6
No abstract yet
Complete cytogenietic remission with imatinib mesylate treatment in chronic myelogenous leukemia (CML) developed after renal transplantation.
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Aloisi A, DI Gregorio S, Stagno F, Guglielmo P, Mannino F, Sormani MP, Bruzzi P, Gambacorti-Passerini C, Saglio G, Venuta S, Giustolisi R, Messina A, Vigneri PG
Blood. 2005 Oct 25;
The BCR-ABL oncoprotein of Chronic Myelogenous Leukemia (CML) localizes to the cell cytoplasm where it activates proliferative and anti-apoptotic signaling pathways. We previously reported that the combination of the ABL kinase inhibitor Imatinib Mesylate (IM) and the nuclear export inhibitor Leptomycin B (LMB) traps BCR-ABL inside the nucleus, triggering the death of the leukemic cells. To evaluate the efficacy of the combination of IM and LMB on human cells we collected CD34-positive cells from 6 healthy donors and myeloid progenitors from 35 CML patients. The sequential addition of IM and LMB generated the strongest reduction in the proliferative potential of the leukemic cells, with limited toxicity to normal myeloid precursors. Furthermore, nested RT-PCR analysis on colonies representative of each experimental condition demonstrated that the combination of IM and LMB was the most effective regimen in reducing the number of BCR-ABL-positive colonies. The efficacy of the two-drug association was independent of the clinical characteristics of the patients. Our results indicate that strategies aimed at the nuclear entrapment of BCR-ABL efficiently kill human leukemic cells, suggesting that the clinical development of this approach could be of significant therapeutic value for newly-diagnosed and IM-resistant CML patients.
BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of Imatinib Mesylate and Leptomycin B.
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Haltrich I, Kost-Alimova M, Kovács G, Kriván G, Dobos M, Imreh S, Fekete G
Magy Onkol. 2005; 49(2): 141-7
Cytogenetic syndrome involving bands 3q21 and 3q26, known as “3q21q26 syndrome” has been observed in adult patients with acute myelogenous leukemia (0.5-2%), chronic myelogenous leukemia in blast crisis (20%), myelodysplastic syndromes and myeloproliferative disorders. In the present study bone marrow samples from two boys (12 and 16 years), diagnosed with CML and AML respectively, were investigated using conventional cytogenetic methods, interphase “multipoint” fluorescence in situ hybridization (FISH), dual color-FISH and multiplex FISH. The “multipoint” FISH analysis identified in de novo childhood AML case an inv(3)(q21q26) and a complex 3q rearrangement including inversion and duplication in the CML case. The “3q21q26 syndrome” is associated with normal or elevated platelet counts with marked abnormalities of megakaryocytopoiesis, involvement of multiple hematopoietic lineages. The affected patients were resistant to conventional chemotherapy and had a short survival. This syndrome is very rare in de novo childhood AML, and simultaneous presence of 3q inversion and duplication, to our knowledge, has not yet been identified in hematological malignancies. The results of our study underline the importance of classical and modern cytogenetic analysis in the diagnosis of hematological malignancies, because in the majority of cases they can provide additional diagnostic information for the clinicians in deciding the best therapeutic approach, precise classification and prognosis of the disease.
[Identification of 3q21q26 syndrome by "multipoint" interphase FISH analyses in childhood myeloid leukemia]
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He Y, Feng SZ, Wang M, Wei JL, Qin TJ, Zhou Z, Zhai WJ, Qiu LG, Han MZ
Zhonghua Xue Ye Xue Za Zhi. 2005 Jul ; 26(7): 389-92
OBJECTIVE: To evaluate the treatment outcome of HLA-identical sibling allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) patients in first chronic phase (CP(1)). METHODS: Fifty-one patients with CML-CP(1) received HLA-identical sibling allo-HSCT with conditioning regimens of TBI plus Cy or Bu plus Cy. Allogeneic peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) were performed for 28 and 23 patients, respectively. The median follow-up duration was 1434 (60 – 4062) days. RESULTS: Fifty (98.0%) patients were successfully engrafted. Transplant-related mortality occurred in 8 (15.7%) patients. Acute graft-versus-host disease (aGVHD) occurred in 35 (68.6%) patients and 11 (21.6%) patients were grade II-IV, while chronic GVHD (cGVHD) did in 17 (37.8%) patients. Five (7.4%) patients relapsed. The 5-year probability of disease-free survival (DFS) was (79.2 +/- 6.4)%. There was no significant difference in 5-year DFS, death rate and treatment related syndromes between the two conditioning regimens (P > 0.05), and in 5-year DFS, relapse rate and death rate between two transplant choices (P > 0.05). However, the rate of relapse was lower in Bu/Cy group (P [HLA-identical sibling allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia in first chronic phase. Analysis of 51 cases.]
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Geng SX, Li YQ, Chen SH, Yang LJ, Yin QS, Wu XL, Zhang XL
Zhonghua Xue Ye Xue Za Zhi. 2005 Jul ; 26(7): 413-6
OBJECTIVE: To analyze peripheral blood naive T cell level, its T cell receptor (TCR) Vbeta repertoire usage profile and clonality for evaluating the recent thymic output function and the expansion feature of TCR Vbeta subfamily T cells in patients with chronic myelogenous leukemia (CML). METHODS: Quantitative detection of T-cell receptor excision DNA circles (TRECs) in peripheral blood mononuclear cells (PBMNC) from 20 cases of CML was preformed by real-time PCR (TaqMan) analysis, and TRECs-number in T-cells was calculated from peripheral blood CD3-positive cell rate. The expression and clonality analysis were detected by RT-PCR and genescan technique in PBMNC from 14 out of the 20 patients. Nine normal individuals served as controls. RESULTS: A dramatic reduction of TRECs value in patients with CML was detected as compared with that in normal controls. The mean value of TRECs was 0.06 +/- 0.16 copy/1000 CD3(+) cells in CML patients while 6.84 +/- 4.71 copies/1000 CD3(+) cells in normal controls (P
[Peripheral blood naive T cell level and its T cell receptor Vbeta repertoire usage profile in patients with chronic myelogenous leukemia.]
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Hu SY, Chen ZX, Gu WY, Cen JN, Zhao Y, Gu M
Zhonghua Xue Ye Xue Za Zhi. 2005 Jul ; 26(7): 417-20
OBJECTIVE: To investigate retinoblastoma (Rb) associated protein 46 (RbAp46) gene expression levels in bone marrow (BM) cells of leukemia patients. METHODS: Real-time quantitative retroverse polymerase chain reaction (QRT-PCR) method was used for detecting RbAp46 expression levels in BM cells of 140 patients with acute leukemia (AL), 13 with chronic myelogenous leukemia in chronic phase (CML-CP), 7 with CML in blast crisis (CML-BC) and 32 with non-leukemic disorders. RESULTS: The M-Estimators of RbAp46 were higher in 98 newly diagnosed ALs and 5 relapsed ALs than in 28 ALs in complete remission (CR) and 32 non-leukemic controls (178.23 and 213.65 vs 85.89 and 88.08, respectively). No statistic difference was found between the CR group and control group, or between the newly diagnosed group and relapsed group. The M-Estimators of RbAp46 in patients with CML-CP was 58.27, similar to that in control, but much lower than that in CML-BC (173.24). Among 98 newly diagnosed ALs, the M-Estimators of RbAp46 in M(3) and M(4) were the lowest in all of the subtypes. Furthermore, the RbAp46 expression levels were not correlated with the expression of the fusion genes of bcr/abl, PML-RARalpha, and multidrug resistant gene (mdr1), but were positively correlated with Wilms’ tumor gene (WT1) expression levels and negatively with AML1/ETO fusion gene expression. CONCLUSION: RbAp46 expression levels in ALs and CML-BC were strikingly higher than that in non-leukemias and CML-CP, and might participate in leukemogenesis.
[Detection of RbAp46 expression in bone marrow cells of leukemia patients by real-time quantitative RT-PCR.]