-
Xiao-Wei Zhang, Xiao-Jing Yan,
Zi-Ren Zhou,
Fei-Fei Yang,
Zi-Yu Wu,
Hong-Bin Sun,
Wen-Xue Liang,
Ai-Xing Song,
Lallemand-Breitenbach Valerie,
Jeanne Marion, [......],
Huai-Yu Yang,
Qiu-Hua Huang,
Guang-Biao Zhou,
Jian-Hua Tong,
Yan Zhang,
Ji-Hui Wu,
Hong-Yu Hu,
Hugues de Thé,
Sai-Juan Chen,
and Zhu Chen
Science 02/2013; 328:240-243. · 31.20 Impact Factor
-
Yang Shen,
Yong-Mei Zhu,
Xing Fan,
Jing-Yi Shi,
Qin-Rong Wang, Xiao-Jing Yan,
Zhao-Hui Gu,
Yan-Yan Wang,
Bing Chen,
Chun-Lei Jiang,
Han Yan,
Fei-Fei Chen,
Hai-Min Chen,
Zhu Chen,
Jie Jin,
Sai-Juan Chen
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)-ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.
Blood 08/2011; 118(20):5593-603. · 9.90 Impact Factor
-
Xiao-Jing Yan,
Jie Xu,
Zhao-Hui Gu,
Chun-Ming Pan,
Gang Lu,
Yang Shen,
Jing-Yi Shi,
Yong-Mei Zhu,
Lin Tang,
Xiao-Wei Zhang,
Wen-Xue Liang,
Jian-Qing Mi,
Huai-Dong Song,
Ke-Qin Li,
Zhu Chen,
Sai-Juan Chen
[show abstract]
[hide abstract]
ABSTRACT: Abnormal epigenetic regulation has been implicated in oncogenesis. We report here the identification of somatic mutations by exome sequencing in acute monocytic leukemia, the M5 subtype of acute myeloid leukemia (AML-M5). We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases. The DNMT3A mutants showed reduced enzymatic activity or aberrant affinity to histone H3 in vitro. Notably, there were alterations of DNA methylation patterns and/or gene expression profiles (such as HOXB genes) in samples with DNMT3A mutations as compared with those without such changes. Leukemias with DNMT3A mutations constituted a group of poor prognosis with elderly disease onset and of promonocytic as well as monocytic predominance among AML-M5 individuals. Screening other leukemia subtypes showed Arg882 alterations in 13.6% of acute myelomonocytic leukemia (AML-M4) cases. Our work suggests a contribution of aberrant DNA methyltransferase activity to the pathogenesis of acute monocytic leukemia and provides a useful new biomarker for relevant cases.
Nature Genetics 03/2011; 43(4):309-15. · 35.53 Impact Factor
-
Xiao-Wei Zhang, Xiao-Jing Yan,
Zi-Ren Zhou,
Fei-Fei Yang,
Zi-Yu Wu,
Hong-Bin Sun,
Wen-Xue Liang,
Ai-Xin Song,
Valérie Lallemand-Breitenbach,
Marion Jeanne, [......],
Huai-Yu Yang,
Qiu-Hua Huang,
Guang-Biao Zhou,
Jian-Hua Tong,
Yan Zhang,
Ji-Hui Wu,
Hong-Yu Hu,
Hugues de Thé,
Sai-Juan Chen,
Zhu Chen
[show abstract]
[hide abstract]
ABSTRACT: Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RARalpha degradation is triggered by their SUMOylation, but the mechanism by which As2O3 induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARalpha and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)-conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As2O3 provides new insights into the drug's mechanism of action and its specificity for APL.
Science 04/2010; 328(5975):240-3. · 31.20 Impact Factor
-
Lan Wang,
Guang-Biao Zhou,
Ping Liu,
Jun-Hong Song,
Yang Liang, Xiao-Jing Yan,
Fang Xu,
Bing-Shun Wang,
Jian-Hua Mao,
Zhi-Xiang Shen,
Sai-Juan Chen,
Zhu Chen
[show abstract]
[hide abstract]
ABSTRACT: To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G(1)/G(0) arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RARalpha degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.
Proceedings of the National Academy of Sciences 04/2008; 105(12):4826-31. · 9.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The title compound, C(20)H(32)N(2)O(2)S(2), has been synthesized by the reaction of α-methyl-sulfanylcyclo-dodeca-none and p-toluene-sulfonyl-hydrazine. In the crystal structure, the conformation of the non-benzenoid ring is [3333] and the methyl-sulfanyl group is in the α-side exo position. The mol-ecules are linked by inter-molecular N-H⋯S hydrogen bonds.
Acta Crystallographica Section E Structure Reports Online 01/2008; 64(Pt 4):o657. · 0.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A method was developed for the determination of 7B3 (12-propyloxyimino-1,15-pentadecanlactam), a novel macrolactam fungicide, by liquid chromatography/mass spectrometry (LC/MS) with positive electrospray ionization (ESI+). The method used a reversed-phase C18 column and acetonitrile-water (60 + 40, v/v) mobile phase. The quick, easy, cheap, effective, rugged, and safe method was used for extraction of 7B3 from cotton plants, which involved the extraction of 10 g homogenized sample with 10 mL acetonitrile, followed by the addition of 4 g anhydrous MgSO4 and 1.0 g NaCl. After centrifugation, 1 mL of the buffered acetonitrile extract was transferred into a tube containing 50 mg primary secondary amine sorbent and 100 mg anhydrous MgSO4. After shaking and centrifugation, the final extract was transferred to an autosampler vial for concurrent analysis by LC/MS. The results of 7B3 determined by LC/MS in the selective ion monitoring mode were linear, and the matrix effect of the method was evaluated. The average recoveries of 7B3 fortified at different levels were within 84.1-100.2%, and the relative standard deviations were <7.5% for all samples analyzed. The method limit of detection and the limit of quantitation values were 0.03 and 0.1 mg/kg, respectively. The proposed method was successfully applied to determine 7B3 residues in practical samples. This method is sensitive, accurate, reliable, simple, and safe.
Journal of AOAC International 92(1):302-6. · 1.20 Impact Factor
