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Jun Qian,
Jiang Lin,
Wei Qian,
Ji-Chun Ma,
Si-Xuan Qian,
Yun Li, Jing Yang,
Jian-Yong Li,
Cui-Zhu Wang,
Hai-Yan Chai,
Xing-Xing Chen,
Zhao-Qun Deng
[show abstract]
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ABSTRACT: MicroRNA miR-378 plays important roles in tumorigenesis by enhancing cell survival, reducing apoptosis, promoting tumor growth, angiogenesis and promoting cell migration and invasion. Abnormal expression of miR-378 has been observed in various types of cancers. The aim of this study was to investigate the expression status of miR-378 and its clinical significance in patients with acute myeloid leukemia (AML) using real-time quantitative PCR. miR-378 overexpression was identified in 26 of 84 (31%) AML patients. The patients with miR-378 overexpression had lower hemoglobin level than those without miR-378 overexpression (66 versus 78g/L, respectively, P=0.010). The frequency of miR-378 overexpression in FAB-M2 subtype was higher than other subtypes (44% versus 20%, P=0.032). Moreover, the frequency of miR-378 overexpression was higher in patients with t(8;21) than in others (64% versus 24%, P=0.012). The status of miR-378 expression was not correlated with the mutations of eight genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and U2AF1). The difference in relapse-free survival was observed between patients with and without miR-378 overexpression (P=0.049). These findings suggest that miR-378 up-regulation is a common event and might have an adverse impact on prognosis in AML.
Leukemia research 04/2013; · 2.36 Impact Factor
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Qin Chen,
Jiang Lin,
Jun Qian,
Zhao-Qun Deng,
Wei Qian, Jing Yang,
Yun Li,
Xing-Xing Chen,
Yu-Juan Ma,
Ji-Chun Ma,
Qing Liu
[show abstract]
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ABSTRACT: Aberrant DNA methylation is a common epigenetic alteration and an important feature in human cancers. The DEAD box polypeptide 43 (DDX43) has been found to be overexpressed in various solid tumors and some hematologic malignancies. In the present study, we investigated the methylation status of the DDX43 promoter in 87 Chinese patients with chronic myeloid leukemia (CML) using real-time quantitative methylation-specific polymerase chain reaction and examined the DDX43 transcript in 35 patients using real-time quantitative polymerase chain reaction. DDX43 promoter hypomethylation was observed in 22 (25.3%) CML patients. No significant correlation was found between the hypomethylation of the DDX43 promoter with the age, sex, white blood cell counts, hemoglobin concentration, platelet counts, and chromosomal abnormalities of CML patients (p>0.05). The frequency of DDX43 hypomethylation in patients in the chronic phase, in the accelerated phase, and in blast crisis was 23.4% (15/64), 25.0% (2/8), and 33.3% (5/15), respectively (p>0.05). There was a significant correlation between DDX43 hypomethylation and DDX43 transcript (r=0.469, p=0.004). Our data suggest that hypomethylation of the DDX43 promoter may be an early and frequent molecular event in the development of CML in Chinese patients.
Genetic Testing and Molecular Biomarkers 03/2013; · 1.11 Impact Factor
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Qin Chen,
Jun Qian,
Jiang Lin, Jing Yang,
Yun Li,
Cui-Zhu Wang,
Hai-Yan Chai,
Xing-Xing Chen,
Zhen Qian,
Ji-Chun Ma,
Ming Zhang
[show abstract]
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ABSTRACT: The aim of this study was to investigate the expression level of the SALL4 gene and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Real-time quantitative PCR (RQ-PCR) was performed to detect the expression level of SALL4 mRNA in bone marrow mononuclear cells (BMMNC) from 35 AML, 12 CML patients and 24 iron deficiency anemia patients as controls. The results indicated that the expression level of SALL4 in AML (0%-14%, median 1.43%) was obviously higher than that in controls (0% - 1%, median 0%) (P < 0.001). SALL4 expression was positive in 65.7% (23/35) AML patients. The frequency of SALL4 expression was in M2 (86.7%, 13/15) > M3 (75.0%, 6/8) > M1 (60.0%, 3/5) > M4 (14.3%, 1/7), and the difference among 4 groups was statistically significant (P = 0.008); there was no correlation of the frequency of SALL4 expression with the age, sex, white blood cell WBC count, hemoglobin concentration, platelet count and chromosomal abnormalities of AML patients (P > 0.05). All the 13 CML cases showed positive expression of SALL4 gene (1% - 128%, median 19.39%), which was higher than that in controls (P < 0.001). The analysis of receiver operating characteristic (ROC) curve showed the area under ROC curve (AUC) of AML and CML were 0.983 (95% confidence interval: 0.95 - 1.017) and 0.997 (95% confidence interval: 0.986 - 1.007) respectively. It is concluded that SALL4 expression is a common molecular event and can be considered as a molecular marker for assisting diagnosis of AML and CML.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 03/2013; 21(2):315-9.
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Jing Yang,
Jun Qian,
Jiang Lin,
Xiao-Fei Yang,
Wei Qian,
Qin Chen,
Dong-Ming Yao,
Cui-Zhu Wang,
Xing-Xing Chen,
Gao-Fei Xiao,
Yu-Juan Ma
[show abstract]
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ABSTRACT: SF3B1, located on chromosome 2q33.1, encodes a core component of RNA-splicing machinery, and its mutation has been described in myelodysplastic syndromes (MDS) characterized with ring sideroblasts (RS). To explore the reliability and sensitivity of the high-resolution melting analysis (HRMA) technique for the identification of the SF3B1 mutations, mutations in 92 patients with MDS were detected in this study. The sensitivity could reach 5%, obviously higher than the 25% of direct DNA sequencing. A low frequency (5.4%) of SF3B1 mutations were identified in patients with MDS, including three cases of K700E, one case of H662Q, and one case of K666M. Further, SF3B1 mutations were more frequently recurrent in the 33% of patients with MDS characterized with RS, whereas in other subtypes of MDS, only 2.3% of patients were detected with SF3B1 mutations (p=0.006). In conclusion, a rapid, reproducible, sensitive, and high-throughput HRMA assay has been established for the scanning of SF3B1 mutations.
Genetic Testing and Molecular Biomarkers 02/2013; · 1.11 Impact Factor
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Jing Yang,
Jun Qian,
Dong-Ming Yao,
Si-Xuan Qian,
Wei Qian,
Jiang Lin,
Gao-Fei Xiao,
Cui-Zhu Wang,
Zhao-Qun Deng,
Ji-Chun Ma,
Xing-Xing Chen
[show abstract]
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ABSTRACT: OBJECTIVE: Somatic mutations of SF3B1 gene have recently been identified in myelodysplastic syndrome and chronic lymphocytic leukemia. The frequency and clinical relevance of SF3B1 mutations have been rarely studied in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The present study was aimed to analyze the frequency of SF3B1 mutations in AML and CML. Designs and Methods High-resolution melting analysis (HRMA) was established to detect the mutation hotspots (codon E622, H662, K666, and K700) of SF3B1 gene in 275 AML and 81 CML patients. RESULTS: Heterozygous SF3B1 mutations were detected in three AML patients by HRMA. Direct DNA sequencing identified one K666T, one K666N and one K700E mutations. All three AML patients had normal karyotypes. One case also had NPM1 and DNMT3A mutations, one had FLT3 internal tandem duplication and DNMT3A mutations, and the other had NPM1 mutation. No SF3B1 mutations were detected in CML patients. CONCLUSIONS: SF3B1 mutation is a rare molecular event in Chinese AML and CML patients.
Clinical biochemistry 02/2013; · 2.02 Impact Factor
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Hai-Yan Chai,
Jun Qian,
Jiang Lin, Jing Yang,
Yun Li,
Cui-Zhu Wang,
Xing-Xing Chen,
Qin Chen,
Zhao-Qun Deng,
Dong-Ming Yao,
Ji-Chun Ma
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ABSTRACT: The purpose of this study was to detect the expression of RAGE-1 transcript in the bone marrow mononuclear cells (BMMNC) from patients with acute myeloid leukemia (AML) and to investigate the relationship of RAGE-1 expression level with clinical variables. The expression level of RAGE-1 gene in BMMNC from 94 newly diagnosed AML patients was measured using RQ-PCR. The relationship between RAGE-1 expression level and clinical parameters (age, sex, blood cell counts, diagnosis and prognosis) was investigated, and the levels of RAGE-1 expression were compared in patients before and after treatment. The results showed that overexpression of RAGE-1 transcript was found in 28% (26/94) AML patients (1.34 - 16.34, median 3.07). No significant difference was observed in sex, age, blood parameters and FAB subtypes between the groups with and without RAGE-1 overexpression. There was also no significant difference in the frequency of RAGE-1 overexpression among different cytogenetic risk groups and among the patients with different types of karyotypes. The level of RAGE-1 transcript significantly decreased in those patients obtained complete remission after treatment. The overall survival of AML patients with RAGE-1 overexpression was similar as that in those without RAGE-1 overexpression. It is concluded that RAGE-1 overexpression is a common event in AML, but has no impact on the prognosis of patients.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2013; 21(1):20-4.
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ABSTRACT: OBJECTIVE: SALL4 gene has been identified to stimulate the expansion of hematopoietic stem cell (HSCs) and enhance the self-renewal of HSCs. Overexpression of SALL4 has been found in several cancers. The present study was aimed to investigate the methylation status of SALL4 promoter region in acute myeloid leukemia (AML). DESIGNS AND METHODS: The methylation status of SALL4 promoter was analyzed in 84 patients with AML using methylation-specific PCR (MSP) and its clinical significance was evaluated. RESULTS: Aberrant hypomethylation of SALL4 gene, which was correlated with SALL4 expression, was found in 17.8% (15/84) cases. The patients with SALL4 hypomethylation had significantly older age and higher WBCs than those without SALL4 hypomethylation. The incidence of SALL4 hypomethylation was higher in M1 subtype than in M2 and other subtypes (50%, 26% and 6%, respectively, P=0.001). SALL4 hypomethylation was associated with cytogenetically intermediate and poor groups. Although survival time of the SALL4-hypomethylated AML was shorter than that of SALL4-methylated group (4 months vs 9 months), the difference was not statistically significant (P= 0.356). CONCLUSIONS: Hypomethylation of SALL4 promoter is a common event and is associated with the intermediate and poor karyotypes in AML.
Clinical biochemistry 11/2012; · 2.02 Impact Factor
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Cui-Zhu Wang,
Jiang Lin,
Jun Qian,
Rui Shao,
Di Xue,
Wei Qian,
Gao-Fei Xiao,
Zhao-Qun Deng, Jing Yang,
Yun Li,
Xing-Xing Chen
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ABSTRACT: OBJECTIVE: Recurrent L265P mutation of myeloid differentiation primary response gene 88 (MYD88) has been identified in a proportion of diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia. The present study was aimed to establish a rapid, sensitive, and reliable method using high-resolution melting analysis (HRMA) to detect MYD88 L265P mutation in DLBCL. DESIGNS AND METHODS: The sensitivity of HRMA in the detection of MYD88 L265P mutation was evaluated. MYD88 L265P mutation was further screened in 120 patients with DLBCL. The results of HRMA were validated by direct DNA sequencing. RESULTS: For the detection of MYD88 L265P mutation, the reproducible maximal sensitivity of HRMA was 5%, higher than that obtained by direct DNA sequencing (25%). Heterozygous MYD88 L265P mutations were identified in 11 (9.2%) DLBCL cases, all of which were diagnosed as non- germinal-center B cell (non-GCB) DLBCL. CONCLUSIONS: The HRMA assay is a rapid, sensitive, reliable, and high-throughput method to screen MYD88 L265P mutation and could be used in clinical diagnostic laboratories.
Clinical biochemistry 11/2012; · 2.02 Impact Factor
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Jiang Lin,
Jun Qian,
Dong-Ming Yao,
Wei Qian, Jing Yang,
Cui-Zhu Wang,
Hai-Yan Chai,
Ji-Chun Ma,
Zhao-Qun Deng,
Yun Li,
Qin Chen
[show abstract]
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ABSTRACT: The abnormalities of SALL4 gene, which encodes a zinc-finger transcription factor and is essential for developmental events, have been found to be involved in tumorigenesis. In this study, we investigated the methylation status of the CpG island of SALL4 promoter region in myelodysplastic syndrome (MDS) using methylation-specific PCR (MSP). Aberrant hypomethylation of SALL4 gene was found in 21.7% (18/83) of the cases analyzed. A significantly positive correlation was identified between the level of SALL4 transcript and the status of SALL4 hypomethylation (R=0.641, P<0.001). No correlation was found between SALL4 hypomethylation and clinical parameters. However, the frequency of SALL4 hypomethylation significantly increased in higher risk MDS (14% in Low/Int-1 versus 39% in Int-2/High, P=0.031). The association between SALL4 hypomethylation and the mutations in three methylation modifiers (IDH1, IDH2 and DNMT3A) was not observed. Although the estimated 50% survival time of the SALL4-hypomethylated group was shorter than that of SALL4-methylated group (11.0 months vs. 20.0 months), the difference was not statistically significant (P=0.430). These findings suggest that hypomethylation of SALL4 promoter is a common event in MDS.
Leukemia research 10/2012; · 2.36 Impact Factor
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Qin Chen,
Jiang Lin,
Dong-ming Yao,
Jun Qian,
Wei Qian, Jing Yang,
Hai-yan Chai,
Ji-Chun Ma,
Zhao-qun Deng,
Cui-zhu Wang,
Yun Li
British Journal of Haematology 05/2012; 158(2):293-6. · 4.94 Impact Factor
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Jiang Lin,
Dong-ming Yao,
Jun Qian,
Qin Chen,
Wei Qian,
Yun Li, Jing Yang,
Cui-zhu Wang,
Hai-yan Chai,
Zhen Qian,
Gao-fei Xiao,
Wen-rong Xu
[show abstract]
[hide abstract]
ABSTRACT: The somatic mutations of isocitrate dehydrogenase genes (IDH1 and IDH2) have been identified in a proportion of hematologic malignancies. We examined IDH1 R132 and IDH2 R140/R172 mutations by high resolution melting analysis and direct sequencing in Chinese patients with different myeloid malignancies including 198 acute myeloid leukemia (AML), 82 myelodysplastic syndrome (MDS), 85 chronic myeloid leukemia, and 57 myeloproliferative neoplasms. IDH1 and IDH2 mutations were found in four (2.0%) and ten (5.0%) AML and in two (2.4%) and three (3.6%) MDS cases, but not in other patients. IDH1 and IDH2 mutations were heterozygous and mutually exclusive. IDH1/2 mutations were significantly more frequently observed in cytogenetically normal AML or MDS compared to those without mutations. There was no difference in overall survival of both AML and MDS patients with or without IDH1/2 mutations (P = 0.177 and 0.407, respectively). In conclusion, IDH1/2 mutations are recurrent but rare molecular aberrations in Chinese AML and MDS.
Annals of Hematology 04/2012; 91(4):519-25. · 2.62 Impact Factor
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Jun Qian,
Dong-Ming Yao,
Jiang Lin,
Wei Qian,
Cui-Zhu Wang,
Hai-Yan Chai, Jing Yang,
Yun Li,
Zhao-Qun Deng,
Ji-Chun Ma,
Xing-Xing Chen
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ABSTRACT: Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms. Mutations in U2AF1 were found in 2.5% (7/275) of AML and 6.3% (6/96) of MDS patients, but in none of 81 CML. All mutations were heterozygous missense mutations affecting codon S34 or Q157. There was no significant association of U2AF1 mutation with blood parameters, FAB subtypes, karyotypes and other gene mutations in AML. The overall survival (OS) of AML patients with U2AF1 mutation (median 3 months) was shorter than those without mutation (median 7 months) (P = 0.035). No difference in the OS was observed between MDS patients with and without U2AF1 mutations. Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS.
PLoS ONE 01/2012; 7(9):e45760. · 4.09 Impact Factor
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Qin Chen,
Jiang Lin,
Jun Qian,
Dong-Ming Yao,
Wei Qian,
Yun Li,
Hai-Yan Chai, Jing Yang,
Cui-Zhu Wang,
Ming Zhang,
Gao-Fei Xiao
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ABSTRACT: The aim of this study was to investigate the expression status of the helicase antigen (HAGE) transcript and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The expression of HAGE cDNA in bone marrow mononuclear cells from AML and CML patients was detected by using real-time quantitative PCR. The resuts indicated that overexpression of HAGE transcript (117.12% - 9842.70%, median 434.96%) was detected in 14.8% (11/74) AML patients. AML patients with HAGE cDNA expression were significantly older than those HAGE-negative patients (median 67 and 45 years, respectively, p = 0.001). HAGE cDNA expression was more frequently present among the patients with acute monoblastic leukemia (M(4) and M(5), 7 of 20, 35.0%), compared to the patients with acute non-monoblastic leukemia (M(1), M(2), M(3) and M(6), 4 of 54, 7.4%) (p = 0.007). 28.6% (8/28) cases with normal karyotypes showed HAGE cDNA overexpression, significantly higher than 7.5% (3 of 40) in those with chromosomal abnormalities (p = 0.041). Overexpression of HAGE transcript was found in 9 (34.6%) CML cases and more frequently observed at accelerated phase and blast crisis (4/4, 100%) than that at chronic phase (5/22, 22.7%) (p = 0.008). It is concluded that HAGE cDNA expression is relevant to specific subtypes of AML and to the progression of CML.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 10/2011; 19(5):1171-5.
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ABSTRACT: The mutations of isocitrate dehydrogenase 1 (IDH1) gene have been identified in a proportion of hematologic malignancies including acute myeloid leukemia (AML). The aim of the present study was to explore the reliability of the high-resolution melting analysis (HRMA) for the identification of IDH1 R132 mutations in AML.
We evaluated the sensitivity of HRMA in the detection of IDH1 R132 mutation and screened IDH1 mutations in 110 AML patients using HRMA. The results of HRMA were validated by direct DNA sequencing.
The reproducible sensitivity of HRMA was 5% for the detection of IDH1 R132 mutation, higher than 10% of direct DNA sequencing. Heterozygous IDH1 mutations were identified in 4 (3.6%) AML cases, which were R132H in 3 cases and R132S in 1 case confirmed by DNA sequencing.
The HRMA is a rapid, accurate, reliable, high-throughput method to screen IDH1 gene mutations.
Clinical biochemistry 07/2011; 44(10-11):779-83. · 2.02 Impact Factor
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British Journal of Haematology 07/2011; 154(1):153-5. · 4.94 Impact Factor
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ABSTRACT: To detect the common mutations (D816V and N822K) of c-kit gene in acute myeloid leukemia (AML) using high-resolution melting analysis (HRM).
HRM analysis was established to screen c-kit mutations in PCR products of c-kit exon 17 in 21 AML patients with t(8;21). PCR products were sequenced to confirm the mutation.
HRM analysis identified an aberrant melting curve in 6 cases (28.6%), which were confirmed by direct DNA sequencing as one D816V mutation and five N822K mutation.
HRM analysis is a convenient, rapid, specific and high-throughput technique for scanning c-kit gene mutation in AML.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 01/2011; 32(1):21-4.
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Jiang Lin,
Dong-ming Yao,
Jun Qian,
Qin Chen,
Wei Qian,
Yun Li, Jing Yang,
Cui-zhu Wang,
Hai-yan Chai,
Zhen Qian,
Gao-fei Xiao,
Wen-rong Xu
[show abstract]
[hide abstract]
ABSTRACT: Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS.
PLoS ONE 01/2011; 6(10):e26906. · 4.09 Impact Factor
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ABSTRACT: Several methods have been established to detect the JAK2 V617F mutation, a frequent event involved in the pathogenesis of myeloproliferative neoplasms (MPNs). High-resolution melt (HRM) analysis is a newly established technique without the requirement of any gel-based post-PCR handling.
An asymmetric PCR with unlabeled specific probe was developed and combined to HRM analysis o screen for JAK2 V617F mutation.
Heterozygous mutation was easily distinguished from homozygous JAK2 for the obvious shape change. Homozygous JAK2 mutant can be also well separated from wild-type JAK2 in the presence of internal temperature calibrators. The easily recognizable and maximal sensitivity of HRM analysis was 5% for the detection of JAK2 V617F mutation, higher than 25% of direct sequencing. In the test of blind screening of 223 samples (111 Ph- MPNs, 60 Ph+ chronic myeloid leukemia, and 52 acute myeloid leukemia), JAK2 V617F mutations were found in 78 (70%) patients with MPNs, but in none with chronic and acute myeloid leukemia. HRM analysis of all cases was fully concordant with the results of PCR-RFLP and direct sequencing.
The HRM method with unlabeled probe could be used as convenient, sensitive and reliable diagnostic test for detection of JAK2 V617F mutation.
Journal of Clinical Laboratory Analysis 01/2011; 25(4):300-4. · 1.38 Impact Factor
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ABSTRACT: Detection of the JAK2 mutation has recently been included under the essential diagnostic criteria for myeloproliferative neoplasm (MPN). High-resolution melt (HRM) curve analysis, a nongel-based, automated system, is introduced as a means of mutation scanning without the requirement of any post-PCR handling.
We studied the sensitivity and reproducibility of LightScanner™ platform in the detection of JAK2 V617F mutation and the availability for diagnostic use in MPN.
The reproducible sensitivity of HRM analysis with LightScanner™ platform was 5% for the detection of JAK2 V617F mutation. In the test of blind screening of 105 samples (48 Ph- MPN and 57 Ph+ chronic myeloid leukemia), the identical judgement was interpreted by two blinded investigators. HRM analysis of all cases was fully concordant with the results of PCR-RFLP and direct sequencing.
The HRM method developed here is an extremely sensitive, accurate and reliable technique and allows high-throughput, fast pre-screening to select for sequencing only those specimens that most likely contain mutant JAK2 V617F allele(s).
Clinica chimica acta; international journal of clinical chemistry 12/2010; 411(23-24):2097-100. · 2.54 Impact Factor
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ABSTRACT: The epigenetic disturbances are recognized as an alternative mechanism contributing to the pathogenesis of acute myeloid leukemia (AML). GTPase regulator associated with focal adhesion kinase (GRAF), a putative tumor suppressor gene, was revealed with mutations and promoter methylation in AML and myelodysplastic syndrome. In this study, we investigated the methylation status of GRAF promoter in Chinese AML patients. Aberrant methylation of GRAF promoter was detected in 66.7% (88/132) of the cases analyzed. The methylation of GRAF gene could be detected in all FAB subtypes and in all cytogenetic risk groups. There were no significant differences in clinical features, FAB subtypes and cytogenetic risk groups between patients with and without GRAF methylation. GRAF transcript was significantly lower in AML group compared to controls (3.30 vs 56.06, P<0.001). Both patients with methylated GRAF gene and those without methylated GRAF gene had significantly lower GRAF transcript than controls (P<0.001). Furthermore, GRAF transcript was significantly lower in patients with methylated GRAF than those without methylated GRAF (1.64 vs 6.42, P=0.005). These findings suggest that the hypermethylation of GRAF promoter might be one of early events in the development of AML.
Leukemia research 11/2010; 35(6):783-6. · 2.36 Impact Factor