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Chieh-Lung Cheng,
Hsin-An Hou,
Ming-Cheng Lee,
Chieh-Yu Liu,
Jie-Yang Jhuang,
Yan-Jun Lai,
Chung-Wu Lin,
Huan-Yuan Chen,
Fu-Tong Liu,
Wen-Chien Chou,
Chien-Yuan Chen,
Jih-Luh Tang,
Ming Yao, Shang-Yi Huang,
Bor-Sheng Ko,
Shang-Ju Wu,
Woei Tsay,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: Alterations of galectin-3 expression are often seen in cancers and may contribute to tumorigenesis, cancer progression and metastasis. The studies concerning clinical implications of galectin-3 expression in patients with acute myeloid leukemia (AML) are scarce. We investigated the expression of LGALS3, the gene encoding galectin-3, in the bone marrow (BM) mononuclear cells from an original cohort comprising 280 adults with primary non-M3 AML. Higher LGALS3 expression was closely associated with older age, French-American-British M4/M5 subtypes, CD14 expression on leukemic cells and PTPN11 mutation, but negatively correlated with CEBPA mutation and FLT3-ITD. Compared to patients with lower LGALS3 expression, those with higher expression had lower complete remission rates, higher primary refractory rates and shorter overall survival. This result was validated in an independent validation cohort. A scoring system incorporating higher LGALS3 expression and eight other risk factors, including age, white blood cell count, cytogenetics, and gene mutations, into survival analysis proved to be very useful to stratify AML patients into different prognostic groups (P<0.001). In conclusion, BM LGALS3 expression may serve as a new biomarker to predict clinical outcome in AML patients and galectin-3 may serve as a potential therapeutic target in those patients with higher expression of this protein.
Blood 02/2013; · 9.90 Impact Factor
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Chien-Yuan Chen,
Aristine Cheng, Shang-Yi Huang,
Wang-Huei Sheng,
Jia-Hau Liu,
Bo-Sheng Ko,
Ming Yao,
Wen-Chien Chou,
Hui-Chi Lin,
Yee-Chun Chen,
Woei Tsay,
Jih-Luh Tang,
Shan-Chwen Chang,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: Perianal infection is a common problem for patients with acute leukemia. However, neutropenia and bleeding tendency are relatively contraindicated to surgical intervention. The epidemiology, microbiology, clinical manifestations and outcomes of perianal infection in leukemic patients are also rarely discussed.
The medical records of 1102 adult patients with acute leukemia at a tertiary medical center in Taiwan between 2001 and 2010 were retrospectively reviewed and analyzed.
The prevalence of perianal infection was 6.7% (74 of 1102) in adult patients with acute leukemia. Twenty-three (31%) of the 74 patients had recurrent episodes of perianal infections. Patients with acute myeloid leukemia had higher recurrent rates than acute lymphoblastic leukemia patients (p = 0.028). More than half (n = 61, 53%) of the perianal infections were caused by gram-negative bacilli, followed by gram-positive cocci (n = 36, 31%), anaerobes (n = 18, 15%) and Candida (n = 1, 1%) from pus culture. Eighteen patients experienced bacteremia (n = 24) or candidemia (n = 1). Overall 41 (68%) of 60 patients had polymicrobial infection. Escherichia coli (25%) was the most common micro-organism isolated, followed by Enterococcus species (22%), Klebsiella pneumoniae (13%), and Bacteroides species (11%). Twenty-five (34%) of 74 patients received surgical intervention. Acute leukemia patients with surgically managed anal fistulas tended to have fewer recurrences (p = 0.067). Four (5%) patients died within 30 days after diagnosis of perianal infection. Univariate analysis of 30-day survival revealed the elderly (≧ 65 years) (p = 0.015) and patients with shock (p<0.001) had worse outcome. Multivariate analysis showed septic shock to be the independent predictive factor of 30-day crude mortality of perianal infections (p = 0.016).
Perianal infections were common and had high recurrence rate in adult patients with acute leukemia. Empirical broad-spectrum antibiotics with anaerobic coverage should be considered. Shock independently predicted 30-day crude mortality. Surgical intervention for perianal infection remains challenging in patients with acute leukemia.
PLoS ONE 01/2013; 8(4):e60624. · 4.09 Impact Factor
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Chien-Yuan Chen,
Chan-Hwei Tai,
Aristine Cheng,
Hung-Chang Wu,
Woei Tsay,
Jia-Hau Liu,
Pey-Ying Chen, Shang-Yi Huang,
Ming Yao,
Jih-Luh Tang,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: BACKGROUND: Clinical characteristics and outcomes of intracranial hemorrhage (ICH) among adult patients with various hematological malignancies are limited. METHODS: A total of 2,574 adult patients diagnosed with hematological malignancies admitted to a single university hospital were enrolled into this study between 2001 and 2010. The clinical characteristics, image reports and outcomes were retrospectively analyzed. RESULTS: A total of 72 patients (48 men and 24 women) with a median age of 56 (range 18 to 86) had an ICH. The overall ICH incidence was 2.8% among adult patients with hematological malignancies. The incidence of ICH was higher in acute myeloid leukemia (AML) patients than in patients with other hematological malignancies (6.3% vs 1.1%, P = 0.001). ICH was more common among patients with central nervous system (CNS) involvement of lymphoma than among patients with CNS involved acute leukemia (P <0.001). Sites of ICH occurrence included the cerebral cortex (60 patients, 83%), basal ganglia (13 patients, 18%), cerebellum (10 patients, 14%), and brainstem (5 patients, 7%). A total of 33 patients (46%) had multifocal hemorrhages. In all, 56 patients (77%) had intraparenchymal hemorrhage, 22 patients (31%) had subdural hemorrhage, 15 patients (21%) had subarachnoid hemorrhage (SAH), and 3 patients (4%) had epidural hemorrhage. A total of 22 patients had 2 or more types of ICH. In all, 46 (64%) patients died of ICH within 30 days of diagnosis, irrespective of the type of hematological malignancy. Multivariate analysis revealed three independent prognostic factors: prolonged prothrombin time (P = 0.008), SAH (P = 0.021), and multifocal cerebral hemorrhage (P = 0.026). CONCLUSIONS: The incidence of ICH in patients with AML is higher than patients with other hematological malignancies. But in those with intracranial malignant disease, patients with CNS involved lymphoma were more prone to ICH than patients with CNS involved acute leukemia. Mortality was similar regardless of the type of hematological malignancy. Neuroimaging studies of the location and type of ICH could assist with prognosis prediction for patients with hematological malignancies.
BMC Medicine 08/2012; 10(1):97. · 6.03 Impact Factor
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Shang-Ju Wu,
Yuan-Yeh Kuo,
Hsin-An Hou,
Li-Yu Li,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Fen-Yu Lee,
Ming-Chih Liu,
Chia-Wen Liu,
Chien-Ting Lin,
Chien-Yuan Chen,
Wen-Chien Chou,
Ming Yao, Shang-Yi Huang,
Bor-Sheng Ko,
Jih-Luh Tang,
Woei Tsay,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: Recurrent somatic mutation of SRSF2, one of the RNA splicing machinery genes, has been identified in a substantial proportion of patients with myelodysplastic syndrome (MDS). However, the clinical and biologic characteristics of MDS with this mutation remain to be addressed. In this study, 34 (14.6%) of the 233 MDS patients were found to have SRSF2 mutation. SRSF2 mutation was closely associated with male sex (P = .001) and older age (P < .001). It occurred concurrently with at least 1 additional mutation in 29 patients (85.3%) and was closely associated with RUNX1, IDH2, and ASXL1 mutations (P = .004, P < .001, and P < .001, respectively). Patients with SRSF2 mutation had an inferior overall survival (P = .010), especially in the lower risk patients. Further exploration showed that the prognostic impact of SRSF2 mutation might be attributed to its close association with old age. Sequential analyses in 173 samples from 66 patients showed that all SRSF2-mutated patients retained their original mutations, whereas none of the SRSF2-wild patients acquired a novel mutation during disease evolution. In conclusion, SRSF2 mutation is associated with distinct clinical and biologic features in MDS patients. It is stable during the clinical course and may play little role in disease progression.
Blood 08/2012; 120(15):3106-11. · 9.90 Impact Factor
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American Journal of Hematology 05/2012; 87(8):837-9. · 4.67 Impact Factor
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ABSTRACT: Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated.
Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes.
Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs.
TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity.
BMC Infectious Diseases 11/2011; 11:324. · 3.12 Impact Factor
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Hsin-An Hou,
Yuan-Yeh Kuo,
Chieh-Yu Liu,
Wen-Chien Chou,
Ming Cheng Lee,
Chien-Yuan Chen,
Liang-In Lin,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Ying-Chieh Chiang, [......],
Chia-Wen Liu,
Jih-Luh Tang,
Ming Yao, Shang-Yi Huang,
Bor-Sheng Ko,
Szu-Chun Hsu,
Shang-Ju Wu,
Woei Tsay,
Yao-Chang Chen,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In the present study of 500 patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3A mutations were positively associated with older age, higher WBC and platelet counts, intermediate-risk and normal cytogenetics, FLT3 internal tandem duplication, and NPM1, PTPN11, and IDH2 mutations, but were negatively associated with CEBPA mutations. Multivariate analysis demonstrated that the DNMT3A mutation was an independent poor prognostic factor for overall survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3A mutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P < .001). Sequential study of 138 patients during the clinical course showed that DNMT3A mutations were stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease.
Blood 11/2011; 119(2):559-68. · 9.90 Impact Factor
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ABSTRACT: Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.
A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.
Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm³ for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.
Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.
BMC Infectious Diseases 09/2011; 11:250. · 3.12 Impact Factor
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Wen-Chien Chou,
Sheng-Chieh Chou,
Chieh-Yu Liu,
Chien-Yuan Chen,
Hsin-An Hou,
Yuan-Yeh Kuo,
Ming-Cheng Lee,
Bor-Sheng Ko,
Jih-Luh Tang,
Ming Yao, [......],
Yao-Chang Chen,
Yi-Chang Chang,
Yi-Yi Kuo,
Kuan-Ting Kuo,
Fen-Yu Lee,
Ming-Chi Liu,
Chia-Wen Liu,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in 486 adult patients with primary AML. TET2 mutation occurred in 13.2% of our patients and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than NPM1(+)/FLT3-ITD(-) or CEBPA(+)). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1, and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into 4 groups with different prognoses (P < .0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution.
Blood 08/2011; 118(14):3803-10. · 9.90 Impact Factor
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ABSTRACT: The incidence of chronic lymphocytic leukemia (CLL) in Taiwan is markedly lower than that in Western countries, but we have seen a drastically increasing trend. We explored this distinct incidence trend of CLL for Taiwanese. The epidemiologic data of CLL for Taiwanese and Caucasian Americans during 1986 to 2005 were obtained from the Taiwan National Cancer Registry and Surveillance, Epidemiology, and End Results Program, respectively. The individual effects of time period and birth cohort on the incidence trends were analyzed using an age-period-cohort model. Although there was a weak period effect corresponding to the increased applications of immunophenotyping in 1991 to 1995 in Taiwan, evidences suggested that the age-adjusted incidence rate of CLL for Taiwanese was continuously increasing during the 20-year period while that for Caucasian Americans remained steady. In addition, a much stronger birth-cohort effect was identified for Taiwanese but not for Caucasian Americans. This effect corresponded to the westernization of lifestyle in Taiwan since 1960. We conclude that, in addition to the ethnic difference of incidence, there is distinct increasing incidence trend of CLL in Taiwan. The strong birth-cohort effect underlying this increasing trend indicates that lifestyles and environmental factors may play a role in the development of CLL for Taiwanese.
Blood 11/2010; 116(22):4430-5. · 9.90 Impact Factor
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Wen-Chien Chou,
Huai-Hsuan Huang,
Hsin-An Hou,
Chien-Yuan Chen,
Jih-Luh Tang,
Ming Yao,
Woei Tsay,
Bor-Sheng Ko,
Shang-Ju Wu, Shang-Yi Huang,
Szu-Chun Hsu,
Yao-Chang Chen,
Yen-Ning Huang,
Yi-Chang Chang,
Fen-Yu Lee,
Min-Chih Liu,
Chia-Wen Liu,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Hwei-Fang Tien
[show abstract]
[hide abstract]
ABSTRACT: Mutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in various myeloid malignancies, but they have not been comprehensively investigated in acute myeloid leukemia (AML). In this study, we analyzed ASXL1 mutations in exon 12 in 501 adults with de novo AML. ASXL1 mutations were detected in 54 patients (10.8%), 8.9% among those with normal karyotype and 12.9% among those with abnormal cytogenetics. The mutation was closely associated with older age, male sex, isolated trisomy 8, RUNX1 mutation, and expression of human leukocyte antigen-DR and CD34, but inversely associated with t(15;17), complex cytogenetics, FLT3-internal tandem duplication, NPM1 mutations, WT1 mutations, and expression of CD33 and CD15. Patients with ASXL1 mutations had a shorter overall survival than patients without, but the mutation was not an independent adverse prognostic factor in multivariate analysis. Sequential analyses showed that the original ASXL1 mutations were lost at relapse and/or refractory status in 2 of the 6 relapsed ASXL1-mutated patients studied, whereas 2 of the 109 ASXL1-wild patients acquired a novel ASXL1 mutation at relapse. In conclusion, AML bearing ASXL1 mutations showed distinct clinical and biological features. The ASXL1 mutation status can change during disease evolution in a few patients.
Blood 11/2010; 116(20):4086-94. · 9.90 Impact Factor
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Canadian family physician Medecin de famille canadien 09/2010; 56(9):889-91. · 1.19 Impact Factor
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ABSTRACT: A case of an extramedullary plasmacytoma (EMP), which presented with a solitary pelvic tumor, is reported. Complete tumor resection was performed, followed by radiation therapy. Our experience demonstrates a satisfactory short-term oncological outcome.
Southern medical journal 08/2010; 103(8):831-3. · 0.92 Impact Factor
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Wen-Chien Chou,
Hsin-An Hou,
Chien-Yuan Chen,
Jih-Luh Tang,
Ming Yao,
Woei Tsay,
Bor-Shen Ko,
Shang-Ju Wu, Shang-Yi Huang,
Szu-Chun Hsu,
Yao-Chang Chen,
Yen-Ning Huang,
Yi-Chang Chang,
Fen-Yu Lee,
Ming-Chi Liu,
Chia-Wen Liu,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Hwei-Fang Tien
[show abstract]
[hide abstract]
ABSTRACT: Mutations of nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase gene (IDH1) have been identified in patients with gliomas. Recent genome-wide screening also revealed IDH1 mutation as a recurrent event in acute myeloid leukemia (AML), but its clinical implications in AML are largely unknown. We analyzed 493 adult Chinese AML patients in Taiwan and found 27 patients (5.5%) harboring this mutation. IDH1 mutation was strongly associated with normal karyotype (8.4%, P = .002), isolated monosomy 8 (P = .043), NPM1 mutation (P < .001), and French-American-British M1 subtype (P < .001), but inversely associated with French-American-British M4 subtype (P = .030) and expression of HLA-DR, CD13, and CD14 (P = .002, .003, and .038, respectively). There was no impact of this mutation on patient survival. Sequential analysis of IDH1 mutation was performed in 130 patients during follow-ups. None of the 112 patients without IDH1 mutation at diagnosis acquired this mutation at relapse. In all 18 IDH1-mutated patients studied, the mutation disappeared in complete remission; the same mutation reappeared in all 11 samples obtained at relapse. We conclude that IDH1 is associated with distinct clinical and biologic characteristics and seems to be very stable during disease evolution.
Blood 04/2010; 115(14):2749-54. · 9.90 Impact Factor
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Hsin-An Hou,
Tai-Chung Huang,
Liang-In Lin,
Chieh-Yu Liu,
Chien-Yuan Chen,
Wen-Chien Chou,
Jih-Luh Tang,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Ying-Chieh Chiang,
Fen-Yu Lee,
Ming-Chih Liu,
Ming Yao, Shang-Yi Huang,
Bor-Sheng Ko,
Szu-Chun Hsu,
Shang-Ju Wu,
Woei Tsay,
Yao-Chang Chen,
Hwei-Fang Tien
[show abstract]
[hide abstract]
ABSTRACT: The impact of WT1 mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1 mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1 mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1 mutation was closely associated with younger age (P < .001), French-American-British M6 subtype (P = .006), and t(7;11)(p15;p15) (P = .003). Multivariate analysis demonstrated that the WT1 mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1 mutation, NPM1/FLT3-ITD, CEBPA mutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P < .001). Sequential analyses were performed on 133 patients. WT1 mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1 mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression.
Blood 04/2010; 115(25):5222-31. · 9.90 Impact Factor
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ABSTRACT: Recently, dynamic contrast-enhanced magnetic resonance imaging has been shown to be a non-invasive technique that provides global and functional imaging of bone marrow angiogenesis in acute myeloid leukemia. To assess the clinical implication of changes in angiogenesis shortly after induction chemotherapy, dynamic contrast-enhanced magnetic resonance imaging was performed prospectively before treatment (day 0) and on day 7 in 80 patients with de novo acute myeloid leukemia. We demonstrated that a post-therapeutic reduction in Peak (negative DeltaPeak) compared with the day 0 value was significantly associated with a higher chance of achieving complete remission, and better overall and disease free survival (P=0.022, 0.003 and 0.007, respectively). Cox's multivariate analysis also identified negative DeltaPeak value as an independent good prognostic factor for overall and disease free survival. Our findings provide evidence that the change of Peak on day 7 relative to pre-treatment levels may be a relevant biomarker for early identification of patients who may fail conventional induction chemotherapy (ClinicalTrials.gov Identifier: NCT00172562).
Haematologica 03/2010; 95(8):1420-4. · 6.42 Impact Factor
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Jih-Luh Tang,
Hsin-An Hou,
Chien-Yuan Chen,
Chieh-Yu Liu,
Wen-Chien Chou,
Mei-Hsuan Tseng,
Chi-Fei Huang,
Fen-Yu Lee,
Ming-Chih Liu,
Ming Yao, Shang-Yi Huang,
Bor-Sheng Ko,
Szu-Chun Hsu,
Shang-Ju Wu,
Woei Tsay,
Yao-Chang Chen,
Liang-In Lin,
Hwei-Fang Tien
[show abstract]
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ABSTRACT: Somatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.
Blood 10/2009; 114(26):5352-61. · 9.90 Impact Factor
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Tiffany Ting-Fang Shih,
Hsin-An Hou,
Chieh-Yu Liu,
Bang-Bin Chen,
Jih-Luh Tang,
Hsuan-Yu Chen,
Shwu-Yuan Wei,
Ming Yao, Shang-Yi Huang,
Wen-Chien Chou,
Szu-Chun Hsu,
Woei Tsay,
Chih-Wei Yu,
Chao-Yu Hsu,
Hwei-Fang Tien,
Pan-Chyr Yang
[show abstract]
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ABSTRACT: Emerging evidence suggests that progression of hematologic malignancies is associated with angiogenesis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide global and functional imaging of tumor angiogenesis. In this study, we performed bone marrow DCE-MRI prospectively at diagnosis and after induction chemotherapy in 78 de novo acute myeloid leukemia (AML) patients and correlated it with treatment outcome. An algorithm to assess bone marrow angiogenesis by measuring the DCE-MRI time-intensity curve pixel by pixel was developed using 3 distinct parameters: peak enhancement ratio (Peak) to indicate tissue blood perfusion; amplitude (Amp) to reflect vascularity; and volume transfer constant (K trans) to indicate vascular permeability. The Peak and Amp decreased significantly at remission status after induction chemotherapy. Patients with higher Peak or Amp at diagnosis had shorter overall survival and disease-free survival than others. Cox multivariate analysis identified higher Peak value (hazard ratio, 9.181; 95% confidence interval, 1.740-48.437; P = .009) as an independent predictor for overall survival in addition to unfavorable karyotype and old age. Our findings provide evidence that increased bone marrow angiogenesis measured by DCE-MRI can predict adverse clinical outcome in AML patients. DCE-MRI may help to select high-risk phenotype AML patients for tailored antiangiogenic therapy and to monitor treatment response.
Blood 12/2008; 113(14):3161-7. · 9.90 Impact Factor
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ABSTRACT: Bortezomib, a proteasome inhibitor, has been clinically approved for the treatment of myeloma and lymphoma. Here, we report a differential effect of bortezomib on apoptosis in four hepatocellular carcinoma (HCC) cell lines and identify the major molecular event that determines sensitivity. Although bortezomib inhibited proteasome activity to a similar extent in all HCC cell lines, it showed differential effects on their viability: Huh-7 (IC(50) 196 nmol/L), Sk-Hep1 (IC(50) 180 nmol/L), Hep3B (IC(50) 112 nmol/L), and resistant PLC5 (IC(50) >1,000 nmol/L). Bortezomib caused cell cycle arrest at G(2)-M phase in all HCC cells tested whereas apoptotic induction was found only in sensitive cells but not in PLC5 cells. No significant bortezomib-induced NF-kappaB changes were noted in Huh-7 and PLC5. Bortezomib down-regulated phospho-Akt (P-Akt) in a dose- and time-dependent manner in all sensitive HCC cells whereas no alterations of P-Akt were found in PLC5. Down-regulation of Akt1 by small interference RNA overcame the apoptotic resistance to bortezomib in PLC5 cells, but a constitutively activated Akt1 protected Huh-7 cells from bortezomib-induced apoptosis. Furthermore, bortezomib showed suppression of tumor growth with down-regulation of P-Akt in Huh-7 tumors but not in PLC5 tumors. Down-regulation of P-Akt represents a major molecular event of bortezomib-induced apoptosis in HCC cell lines and may be a biomarker for predicting clinical response to HCC treatment. Targeting Akt signaling overcomes drug resistance to bortezomib in HCC cells, which provides a new approach for the combinational therapy of HCC.
Cancer Research 09/2008; 68(16):6698-707. · 7.86 Impact Factor
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ABSTRACT: Conventional sonography (CS) had many unwanted artifacts, which obscured the carotid artery lesions. We try to explore whether the combination of tissue harmonic imaging (THI), real-time spatial compound sonography (SCS), and adaptive image processing (AIP) techniques (CTX) could be a better way to reduce the artifacts in the carotid artery and enhance the visualization of its plaques and intima-medial thickness (IMT) than CS.
Eighty-three patients who harbored IMT (73) and carotid plaques (19) with variable degrees of stenosis underwent scanning for which five different ultrasound techniques were performed for overall image quality, lesion conspicuity, and elimination of artifacts. Two observers, who were blinded to the imaging techniques, graded the different images. A Friedman test was used for multiple statistical comparisons between the five techniques. To make paired comparisons between different imaging modes, Wilcoxon's signed-rank test was used.
The mean Kappa score for the two independent observers was 0.812 (standard error, 0.021), and reflected moderate-to-high interobserver agreement. Combining SCS+THI+AIP (CTX) provided the best for overall image quality, lesion conspicuity, and elimination of undesired artifacts of carotid plaques whereas CS produced the worst quality (p<0.001). There were significant differences among the five techniques (p<0.001); however, there were no differences between SCS and THI on either image quality (p=0.417), lesion conspicuity (p=0.594), or elimination of artifact (p=0.064).
The combined technique of SCS, THI, and AIP may represent the optimal ultrasonic technique for the evaluation of the IMT and carotid plaque echomorphology.
European journal of radiology 05/2008; 71(1):11-6. · 2.65 Impact Factor
