Posted by rob on August 22, 2010 under Uncategorized | 
[Expression of growth-factor independence 1 in patients with leukemia and its significance.]
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Jul;18(4):834-7
Authors: Wang TT, Chen ZX, Cen JN, He J, Sheng HJ, Yao L
This study was purposed to investigate the expression of the growth-factor independence 1 (GFI1) in patients with leukemia and its clinical significance. Bone marrow mononuclear cells were obtained from 65 newly diagnosed leukemia patients including 24 acute myeloid leukemia (AML), 18 chronic myelogenous leukemia (CML), 6 acute lymphoblastic leukemia (ALL), 17 blast crisis of chronic myelogenous leukemia and 13 patients with iron deficiency anemia (IDA) were used as controls. The relative expression of gene gfi1 was detected by reverse transcriptase-polyme-rase chain reaction (RT-PCR) and taqman quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). The results showed that gene expression of gene gfi1 in leukemia patients was obviously higher than that in controls and the difference was statistically significant (p < 0.01), in which the expression of gene gfi1 in newly diagnosed CML patients was higher than that in newly diagnosed AML, newly diagnosed ALL, CML-BCP patients and the difference was significant (p < 0.01). Expression of gene gfi1 in lymphocytic blast crisis of CML was higher than that in nonlymphocytic blast crisis of CML, and the difference was significant. It is concluded that gene gfi1 may play an important role in leukemia, especically in CML incidence and progression. The high level expression of gene gfi1 may be participate in the development of lymphoma.
PMID: 20723283 [PubMed - in process]
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Establishment of the 1st World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA.
Blood. 2010 Aug 18;
Authors: White HE, Matejtschuk P, Rigsby P, Gabert J, Lin F, Wang YL, Branford S, Müller MC, Beaufils N, Beillard E, Colomer D, Dvorakova D, Ehrencrona H, Goh HG, El Housni H, Jones D, Kairisto V, Kamel-Reid S, Kim DW, Langabeer S, Ma ES, Press RD, Romeo G, Wang L, Zoi K, Hughes T, Saglio G, Hochhaus A, Goldman JM, Metcalfe P, Cross NC
Serial quantitation of BCR-ABL mRNA levels is an important indicator of therapeutic response for patients with chronic myelogenous leukemia and Philadelphia-chromosome positive acute lymphoblastic leukemia, but there is substantial variation in the real time quantitative PCR (RQ-PCR) methodologies that are employed by different testing laboratories. To help improve the comparability of results between centers we sought to develop accredited reference reagents that are directly linked to the BCR-ABL international scale. Following assessment of candidate cell lines, a reference material panel comprising four different dilution levels of freeze dried preparations of K562 cells diluted in HL60 cells was prepared. Following performance evaluation, the materials were assigned fixed % BCR-ABL/control gene values according to the International Scale. A recommendation that the four materials be established as the 1st World Health Organization (WHO) International Genetic Reference Panel for quantitation of BCR-ABL translocation by RQ-PCR was approved by the Expert Committee on Biological Standardization of the WHO in November 2009. We consider that the development of these reagents is a significant milestone in the standardization of this clinically important test, but since they are a limited resource we suggest that their availability is restricted to manufacturers of secondary reference materials.
PMID: 20720184 [PubMed - as supplied by publisher]
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First-line therapy for chronic myeloid leukemia: new horizons and an update.
Clin Lymphoma Myeloma Leuk. 2010 Jun;10(3):169-76
Authors: Saglio G, Baccarani M
Although imatinib has shown unprecedented efficacy in the treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML), approximately one third of patients could benefit from a more effective treatment strategy. Several trials of next-generation agents and modified imatinib-based treatments are in progress, with the aim of improving on standard imatinib 400 mg per day therapy. In the post-imatinib era, a range of assessments are available for evaluating novel strategies. Based on existing evidence, achieving a complete cytogenetic response (CCyR) within 12 months provides the best prediction of longer-term benefit, although durable response and freedom from disease progression are the main treatment goals. In phase II studies, first-line treatment with dasatinib 100 mg once daily or nilotinib 400 mg twice daily resulted in high rates of CCyR and major molecular response (MMR) compared with historical data, and separate phase III trials are ongoing to compare each of these agents with imatinib for the treatment of newly diagnosed CP-CML. Preliminary results indicated higher 12-month CCyR and MMR and lower progression rates for nilotinib compared with standard-dose imatinib. Conflicting findings were reported regarding the ability of high-dose imatinib (800 mg per day) or imatinib plus interferon to induce higher response rates compared with standard-dose imatinib, although no improvement in progression-free survival or overall survival was reported. In the absence of trials comparing novel strategies, the synthesis of emerging data from next-generation agents and modified imatinib-based strategies is likely to be a key area of debate during the next few years.
PMID: 20511160 [PubMed - indexed for MEDLINE]
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Expression of oncogenic kinase Bcr-Abl impairs mitotic checkpoint and promotes aberrant divisions and resistance to microtubule-targeting agents.
Mol Cancer Ther. 2010 May;9(5):1328-38
Authors: Wolanin K, Magalska A, Kusio-Kobialka M, Podszywalow-Bartnicka P, Vejda S, McKenna SL, Mosieniak G, Sikora E, Piwocka K
Recent findings showed that BRCA1, in addition to its role in DNA damage response, acts as an upstream regulator of genes involved in the mitotic checkpoint regulation, thus protecting against promotion of aberrant divisions and aneuploidy. Moreover, there is also an indication that the BRCA1 protein is downregulated in chronic myeloid leukemia (CML) patients. We have investigated a possible functional relationship between BRCA1 and mitotic checkpoint competence in cells with the same genetic background expressing different levels of Bcr-Abl, an oncogene responsible for CML. Herein, we show that Bcr-Abl strongly downregulates the BRCA1 protein level, which is partially reversed on treatment with imatinib, an inhibitor of Bcr-Abl tyrosine kinase. Bcr-Abl leads to decreased expression of genes involved in the mitotic checkpoint activation–Mad2, Bub1, Bub3, and BubR1, resulting in mitosis perturbances, weakened mitotic checkpoint function, and mitotic slippage after nocodazole treatment. Furthermore, high Bcr-Abl-expressing cells showed also postmitotic checkpoint dysfunctions and inability to effectively arrest in the 4NG1 phase of the cell cycle, which was associated with limited p21 induction. These observations had significant biological consequences, as we found a high level of improper divisions, chromosomal missegregation, and generation of polyploid cells on mitotic checkpoint prolonged activation. Additionally, Bcr-Abl-expressing cells showed resistance to death activated by spindle defects, reversed by imatinib. Our study presents new facts and supports the hypothesis concerning the mutator nature of Bcr-Abl itself. The functional interaction between Bcr-Abl and mitosis dysfunctions, due to compromised mitotic checkpoints, may have important implications for the generation of aneuploidy and CML progression.
PMID: 20442314 [PubMed - indexed for MEDLINE]
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The combination of thymosin and methylprednisolone for the treatment of a patient with colonic ulcers, subcutaneous nodules, and pleural effusion after dasatinib treatment for chronic myeloid leukemia.
Leuk Lymphoma. 2010 May;51(5):941-3
Authors: Chen J, Zheng Z, Shen J, Zhou Y
PMID: 20350280 [PubMed - indexed for MEDLINE]
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Co-expression of HoxA9 and bcr-abl genes in chronic myeloid leukemia.
Leuk Lymphoma. 2010 May;51(5):892-6
Authors: Tedeschi FA, Cardozo MA, Valentini R, Zalazar FE
We have analyzed the co-expression of the bcr-abl and HoxA9 genes in the follow-up of patients with chronic myeloid leukemia (CML). In the present work we measured the HoxA9 and bcr-abl gene expression in sequential samples. In all patients, bcr-abl and HoxA9 were expressed at detectable levels in every sample. When the results were expressed in relation to abl, two different situations were found: (a) patients clinically stable at second sampling, with low relative risk at diagnosis (low Sokal’s score), did not show significant differences in both bcr-abl and HoxA9 levels in the sequential samples analyzed, and (b) patients with poor prognosis (showing intermediate or high Sokal’s score at diagnosis) had increased expression of bcr-abl as well as HoxA9 genes (p < 0.05). Since HoxA9 gene expression remains at relatively constant levels throughout adult life, our results could reflect actual changes in the expression rate of this gene associated with bcr-abl during the progression of CML.
PMID: 20141430 [PubMed - indexed for MEDLINE]
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