Low frequency of mutations in Chinese with acute myeloid leukemia: Different disease or different aetiology?

Yin, Jiawei; Xie, Xiaoli; Zhang, Fan; Chen, Zheng; Hu, Chenxi; Su, Guanghao; Liu, Hong; Zheng, Yuanna; He, Chao; Shen, Hongjie; Qiu, Qiao‐Cheng; He, Jun; Pan, Zhongbin; Gale, Robert Peter; Wu, Depei; Yin, Bin

doi:10.1016/j.leukres.2015.03.002

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…There were no homozygous mutant sequences at the R882 site. Consistent with a study in Suzhou, China, the R882 mutation rate in DNMT3A was 6% (95% CI, 3–9%) in 269 AML patients (Yin et al, ). However, the mutation frequency in Western counties was much higher than that in our present study, ranging from 17.8% to 23% in Caucasian AML patients (Abdelwahab and Levine, ).…”

Section: Discussionsupporting

confidence: 83%

Do mutations in DNMT3A/3B affect global DNA hypomethylation among benzene‐exposed workers in Southeast China?: Effects of mutations in DNMT3A/3B on global DNA hypomethylation

Zhang

et al. 2017

Environ and Mol Mutagen

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Global DNA hypomethylation is commonly observed in benzene-exposed workers, but the underlying mechanisms remain unclear. We sought to discover the relationships among reduced white blood cell (WBC) counts, micronuclear (MN) frequency, and global DNA methylation to determine whether there were associations with mutations in DNMT3A/3B. Therefore, we recruited 410 shoe factory workers and 102 controls from Wenzhou in Zhenjiang Province. A Methylated DNA Quantification Kit was used to quantify global DNA methylation, and single nucleotide polymorphisms (SNPs) in DNMT3A (rs36012910, rs1550117, and R882) and DNMT3B (rs1569686, rs2424909, and rs2424913) were identified using the restriction fragment length polymorphism method. A multilinear regression analysis demonstrated that the benzene-exposed workers experienced significant global DNA hypomethylation compared with the controls (β = -0.51, 95% CI: -0.69 to -0.32, P < 0.001). The DNMT3A R882 mutant allele (R882H and R882C) (β = -0.25, 95% CI: -0.54 to 0.04, P = 0.094) and the DNMT3B rs2424909 GG allele (β = -0.37, 95% CI: -0.70 to -0.03, P = 0.031) were significantly associated with global DNA hypomethylation compared with the wild-type genotype after adjusting for confounding factors. Furthermore, the MN frequency in the R882 mutant allele (R882H and R882C) (FR = 1.18, 95% CI: 0.99 to 1.40, P = 0.054) was higher than that of the wild-type. The results imply that hypomethylation occurs due to benzene exposure and that mutations in DNMTs are significantly associated with global DNA methylation, which might have influenced the induction of MN following exposure to benzene. Environ. Mol. Mutagen. 58:678-687, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 83%

Do mutations in DNMT3A/3B affect global DNA hypomethylation among benzene‐exposed workers in Southeast China?: Effects of mutations in DNMT3A/3B on global DNA hypomethylation

Zhang

et al. 2017

Environ and Mol Mutagen

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“…The internal tandem duplications of FLT3 ( FLT3 -ITD) were tested as described [ 55 , 77 ]. Briefly, the fragment from exon 14 to exon 15 of FLT3 were amplified using previously described primers ( Supplementary Table S1 ) [ 78 ] from genomic DNA by the following steps: denaturing at 94°C for 45 seconds, annealing at 57°C for 45 seconds, and extension at, 72°C for 30 seconds, for 35 cycles on a Master cycler® pro (Eppendorf, Germany) including a pre-denaturation at 94°C and a post-extension at 72°C for 5 minutes, respectively.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients

et al. 2016

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DNMT3A mutation is known as a recurrent event in acute myelogenous leukemia (AML) patients. However, association between DNMT3A genetic polymorphisms and AML patients' outcomes is unknown. DNMT3A 11 SNPs (rs11695471, rs2289195, rs734693, rs2276598, rs1465825, rs7590760, rs13401241, rs7581217, rs749131, rs41284843 and rs7560488) were genotyped in 344 diagnostic non-FAB-M3 AML patients from southern China. Patients underwent combined chemotherapy with cytarabine and anthracyclines. DNMT3A mRNA expression was analyzed in PBMCs from randomly selected AML patients. Multivariate analysis and combined genotype analysis showed that rs2276598 was associated with increased while rs11695471 and rs734693 were associated with decreased chemosensitivity (P<0.05), while rs11695471 (worse for OS), rs2289195 (favorable for OS and DFS) and rs2276598 (favorable for DFS) were significantly associated with disease prognosis (P<0.05). In conclusion, DNMT3A polymorphisms may be potential predictive markers for AML patients' outcomes, which might improve prognostic stratification of AML.

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“…Third, median age of our study subjects was 36 years compared with 49 and 43 years in the HOVON-SAKK and ALSG trials (4,6). Fourth, there may be differences in cytogenetics and/or mutation topography of AML between Chinese and persons of predominately European descent (31,32). Eighty-nine percent subjects in our trial were in favorable and intermediate risk group, which was higher than other randomized clinical trials.…”

Section: Discussionmentioning

confidence: 76%

Randomized Trial of Intermediate-dose Cytarabine in Induction and Consolidation Therapy in Adults with Acute Myeloid Leukemia

Wei

Wang

Gale

et al. 2020

Clinical Cancer Research

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Purpose: Cytarabine, 100-200 mg/mEþ2/day, is commonly used in induction therapy of acute myelogenous leukemia (AML). Whether a higher dose of cytarabine would be more effective is unknown. Also, there is controversy whether high-dose cytarabine is better than an intermediate-dose combined with other drugs for post-remission therapy. In this open-label, randomized controlled, parallel group study, roles of intermediate-dose cytarabine were investigated.Patients and Methods: Subjects with AML age 15-55 years were randomized to receive daunorubicin, omacetaxine mepesuccinate, and conventional-or intermediate-dose cytarabine. Subjects achieving complete remission were randomized to receive 3 courses of high-dose cytarabine or 2 courses of intermediate-dose cytarabine with daunorubicin in the 1 st and mitoxantrone in the 2 nd course. The primary endpoint was disease-free survival (DFS). Results: 591 subjects were randomized to intermediate-(N ¼ 295) or conventional-dose (N ¼ 296) cytarabine group. Threeyear DFSs were 67% [95% confidence interval (CI), 61-73] in the intermediate-dose cohort compared with 54% (95% CI, 48-61) in the conventional-dose cohort [Hazard Ratio (HR), 0.67; 95%CI, 0.51-0.89; P ¼ 0.005). Three-year survivals were 68% (95%CI, 63-74) and 59% (95%CI, 53-65; HR, 0.720; 95%CI, 0.56-0.94; P ¼ 0.014). Two courses of intermediate-dose cytarabine with daunorubicin or mitoxantrone resulted in similar DFS and survival as three courses of high-dose cytarabine when used for postremission therapy. Conclusions: Induction therapy with intermediate-dose cytarabine with daunorubicin and omacetaxine mepesuccinate increases DFS and survival in persons with AML ages 15-55 years compared with conventional-dose cytarabine. See related commentary by Watts and Bradley, p. 3073 Patients and Methods Study design and participantsThis study was an open-label, randomized controlled, parallel group single-center trial conducted at the Blood Disease Hospital, Chinese

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Low frequency of mutations in Chinese with acute myeloid leukemia: Different disease or different aetiology?

Cited by 7 publications

References 27 publications

Do mutations in DNMT3A/3B affect global DNA hypomethylation among benzene‐exposed workers in Southeast China?: Effects of mutations in DNMT3A/3B on global DNA hypomethylation

Do mutations in DNMT3A/3B affect global DNA hypomethylation among benzene‐exposed workers in Southeast China?: Effects of mutations in DNMT3A/3B on global DNA hypomethylation

Evaluation of DNMT3A genetic polymorphisms as outcome predictors in AML patients

Randomized Trial of Intermediate-dose Cytarabine in Induction and Consolidation Therapy in Adults with Acute Myeloid Leukemia

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