Abstract:
:The gene for the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which is closely related with cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation in several human cancers, including malignant lymphoma. Promoter hypermethylation of the MGMT gene is a favorable prognostic factor in diffuse large B-cell lymphoma (DLBCL). Although inactivation of the MGMT gene is closely related to p53 gene mutations in several cancers, the relationship between p53 gene mutation and MGMT inactivation in malignant lymphoma has not been thoroughly examined. We studied the correlation between MGMT hypermethylation and p53 mutation in DLBCL and their impacts on patient prognosis. In a retrospective cohort study, we used a methylation-specific polymerase chain reaction technique to analyze the methylation status of the promoter region of the MGMT gene in 116 DLBCL patients who received cyclophosphamide as part of multidrug combination chemotherapies. Denaturing high-performance liquid chromatography and direct sequencing were used to search for p53 gene mutations in exons 5 through 9 in 96 of the 116 samples. Disease-free survival and overall survival were estimated by the Kaplan-Meier method. Multivariate survival analyses were performed with the Cox proportional hazards model. Forty-five (38.8%) of 116 DLBCL patients showed MGMT promoter hypermethylation. The presence of MGMT hypermethylation was associated with better overall survival (P = .036). MGMT promoter hypermethylation was a prognostic factor that was independent of established prognostic factors, such as age, disease stage, serum lactic dehydrogenase level, and the number of extranodal disease sites (hazard ratio, 2.43; 95% confidence interval, 1.28-4.61; P = .007). p53 mutations were detected in 19 (19.8%) of 96 patients and were identified as a risk factor in the complete remission rate and overall survival (P = .0040, and P = .027, respectively). A correlation between MGMT hypermethylation and p53 mutation or p53 G:C-to-A:T mutation was not observed (P = .88, and P = .31, respectively). MGMT promoter hypermethylation and p53 mutation are useful prognostic markers in DLBCL. The impact of MGMT inactivation on p53 mutation in DLBCL is unclear.
journal_name
Int J Hematoljournal_title
International journal of hematologyauthors
Hiraga J,Kinoshita T,Ohno T,Mori N,Ohashi H,Fukami S,Noda A,Ichikawa A,Naoe Tdoi
10.1532/IJH97.06087subject
Has Abstractpub_date
2006-10-01 00:00:00pages
248-55issue
3eissn
0925-5710issn
1865-3774pii
U813274V78J55UTNjournal_volume
84pub_type
杂志文章abstract::A patient with myeloid/natural killer (NK) cell precursor acute leukemia who was also homozygous for protein C deficiency was treated and showed a complete remission while he simultaneously received low molecular weight heparin. He presented with fever spikes, lymphadenopathy, and a bulky tumor of the anterior mediast...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/BF02983384
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abstract::We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia refractory to immunosuppressive therapy. In one patient, hemoglobin levels increased f...
journal_title:International journal of hematology
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journal_title:International journal of hematology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2018-11-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-012-1256-x
更新日期:2013-02-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-011-0884-x
更新日期:2011-07-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-010-0763-x
更新日期:2011-02-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1532/ijh97.04017
更新日期:2004-10-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
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journal_title:International journal of hematology
pub_type: 杂志文章
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journal_title:International journal of hematology
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-013-1483-9
更新日期:2014-01-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-009-0392-4
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journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1007/s12185-013-1323-y
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journal_title:International journal of hematology
pub_type: 杂志文章
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更新日期:2002-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-10-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s12185-017-2271-8
更新日期:2017-10-01 00:00:00
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journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-009-0404-4
更新日期:2009-10-01 00:00:00
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journal_title:International journal of hematology
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:
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journal_title:International journal of hematology
pub_type: 杂志文章,评审
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journal_title:International journal of hematology
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2015-05-01 00:00:00