14 results on '"Hsin An Hou"'
Search Results
2. Comparison of the 2022 world health organization classification and international consensus classification in myelodysplastic syndromes/neoplasms
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Wan-Hsuan Lee, Chien-Chin Lin, Cheng-Hong Tsai, Feng-Ming Tien, Min-Yen Lo, Mei-Hsuan Tseng, Yuan-Yeh Kuo, Shan-Chi Yu, Ming-Chih Liu, Chang-Tsu Yuan, Yi-Tsung Yang, Ming-Kai Chuang, Bor-Sheng Ko, Jih-Luh Tang, Hsun-I Sun, Yi-Kuang Chuang, Hwei-Fang Tien, Hsin-An Hou, and Wen-Chien Chou
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization (WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification.
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- 2024
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3. Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame mutations
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Feng-Ming Tien, Chi-Yuan Yao, Xavier Cheng-Hong Tsai, Min-Yen Lo, Chien-Yuan Chen, Wan-Hsuan Lee, Chien-Chin Lin, Yuan-Yeh Kuo, Yen-Ling Peng, Mei-Hsuan Tseng, Yu-Sin Wu, Ming-Chih Liu, Liang-In Lin, Ming-Kai Chuang, Bor-Sheng Ko, Ming Yao, Jih-Luh Tang, Wen-Chien Chou, Hsin-An Hou, and Hwei-Fang Tien
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPA bZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPA bZIP-inf. One hundred and thirteen CEBPA bZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPA bZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPA bZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPA bZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control.
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- 2024
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4. Validation of the molecular international prognostic scoring system in patients with myelodysplastic syndromes defined by international consensus classification
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Wan-Hsuan Lee, Ming-Tao Tsai, Cheng-Hong Tsai, Feng-Ming Tien, Min-Yen Lo, Mei-Hsuan Tseng, Yuan-Yeh Kuo, Ming-Chih Liu, Yi-Tsung Yang, Jui-Che Chen, Jih-Luh Tang, Hsun-I Sun, Yi-Kuang Chuang, Liang-In Lin, Wen-Chien Chou, Chien-Chin Lin, Hsin-An Hou, and Hwei-Fang Tien
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R). Overall, 42.5% of the patients were reclassified and 29.3% were up-staged from the IPSS-R. After the reclassification, 16.9% of the patients may receive different treatment strategies. The IPSS-M had greater discriminative potential than the IPSS-R and IPSS. Patients with high, or very high-risk IPSS-M might benefit from allogeneic hematopoietic stem cell transplantation. IPSS-M, age, ferritin level, and the 2022 ICC categorization predicted outcomes independently. After analyzing demographic and genetic features, complementary genetic analyses, including KMT2A-PTD, were suggested for accurate IPSS-M categorization of patients with ASXL1, TET2, STAG2, RUNX1, SF3B1, SRSF2, DNMT3A, U2AF1, and BCOR mutations and those classified as MDS, not otherwise specified with single lineage dysplasia/multi-lineage dysplasia based on the 2022 ICC. This study confirmed that the IPSS-M can better risk-stratified MDS patients for optimized therapeutic decision-making.
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- 2023
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5. Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML
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Xavier Cheng-Hong Tsai, Kuo-Jui Sun, Min-Yen Lo, Feng-Ming Tien, Yuan-Yeh Kuo, Mei-Hsuan Tseng, Yen-Ling Peng, Yi-Kuang Chuang, Bor-Sheng Ko, Jih-Luh Tang, Hsun-I Sun, Ming-Chih Liu, Chia-Wen Liu, Chien-Chin Lin, Ming Yao, Wen-Chien Chou, Hsin-An Hou, and Hwei-Fang Tien
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age
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- 2023
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6. ASXL1 mutation confers poor prognosis in primary myelofibrosis patients with low JAK2V617F allele burden but not in those with high allele burden
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Yuan-Yeh Kuo, Ming Yao, Yu-Hung Wang, Fen-Ming Tien, Hwei-Fang Tien, Ko-Ping Chang, Yun-Chu Lin, Chung-Wu Lin, Jih-Luh Tang, Sze-Hwei Lee, Tai-Chung Huang, Hsin-An Hou, Cheng-Hong Tsai, Chien-Chin Lin, Wen-Chien Chou, and Shan-Ju Wu
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Oncology ,Male ,medicine.medical_specialty ,Poor prognosis ,Mutation, Missense ,Myeloproliferative disease ,lcsh:RC254-282 ,Disease-Free Survival ,Internal medicine ,Correspondence ,medicine ,Humans ,Allele ,Myelofibrosis ,Cancer genetics ,Alleles ,Aged ,Retrospective Studies ,business.industry ,Hematology ,Janus Kinase 2 ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Repressor Proteins ,Survival Rate ,Amino Acid Substitution ,Primary Myelofibrosis ,Mutation (genetic algorithm) ,Female ,business - Published
- 2020
7. The prognostic significance of global aberrant alternative splicing in patients with myelodysplastic syndrome
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Chien-Chin Lin, Cheng-Hong Tsai, Chein-Jun Kao, Hsin-An Hou, Hwei-Fang Tien, Mei-Hsuan Tseng, Yu-Chiao Chiu, Wen-Chien Chou, and Yi-Tsung Yang
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Kaplan-Meier Estimate ,Protein degradation ,lcsh:RC254-282 ,Article ,Transcriptome ,03 medical and health sciences ,Internal medicine ,Medicine ,Humans ,Prospective cohort study ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Proportional hazards model ,Gene Expression Profiling ,Alternative splicing ,EZH2 ,Computational Biology ,Reproducibility of Results ,Hematology ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Gene expression profiling ,Alternative Splicing ,030104 developmental biology ,International Prognostic Scoring System ,Myelodysplastic Syndromes ,Female ,business ,Biomarkers - Abstract
Aberrant alternative splicing (AS) is a hallmark of cancer development. However, there are limited data regarding its clinical implications in myelodysplastic syndrome (MDS). In this study, we performed an in-depth analysis of global AS in 176 primary MDS patients with 20 normal marrow transplant donors as reference. We found that 26.9% of the expressed genes genome-wide were aberrantly spliced in MDS patients compared with normal donors. These aberrant AS genes were related to pathways involved in cell proliferation, cell adhesion and protein degradation. A higher degree of global aberrant AS was associated with male gender and U2AF1 mutation, and predicted shorter overall survival and time to leukemic change. Moreover, it was an independent unfavorable prognostic factor irrespective of age, revised international prognostic scoring system (IPSS-R) risk, and mutations in SRSF2, ZRSR2, ASXL1, TP53, and EZH2. With LASSO-Cox regression method, we constructed a simple prognosis prediction model composed of 13 aberrant AS genes, and demonstrated that it could well stratify MDS patients into distinct risk groups. To our knowledge, this is the first report demonstrating significant prognostic impacts of aberrant splicing on MDS patients. Further prospective studies in larger cohorts are needed to confirm our observations.
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- 2018
8. GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations in adult acute myeloid leukemia
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Hsin-An Hou, Shang-Ju Wu, Shang-Yi Huang, Feng-Ming Tien, Xiu-Wen Liao, Ming Yao, Yuan-Yeh Kuo, Cheng-Hong Tsai, Chia-Wen Liu, Mei-Hsuan Tseng, Yu-Chiao Chiu, Wen-Chien Chou, Chien-Ting Lin, Hwei-Fang Tien, Chien-Yuan Chen, Ming-Chih Liu, Yen-Ling Peng, Liang-In Lin, Szu-Chun Hsu, Bor-Sheng Ko, and Jih-Luh Tang
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0301 basic medicine ,Male ,Myeloid ,DNA Mutational Analysis ,Kaplan-Meier Estimate ,medicine.disease_cause ,0302 clinical medicine ,CEBPA ,Antineoplastic Combined Chemotherapy Protocols ,Zinc finger ,Aged, 80 and over ,Mutation ,GATA2 ,Zinc Fingers ,Hematology ,Exons ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,GATA2 Transcription Factor ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Nucleophosmin ,Adult ,NPM1 ,Karyotype ,Biology ,Polymorphism, Single Nucleotide ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Young Adult ,medicine ,Biomarkers, Tumor ,Humans ,Protein Interaction Domains and Motifs ,Aged ,Neoplasm Staging ,Computational Biology ,Adult Acute Myeloid Leukemia ,Molecular Sequence Annotation ,medicine.disease ,030104 developmental biology ,Cancer research ,Neoplasm Grading - Abstract
Mutations of the GATA binding protein 2 (GATA2) gene in myeloid malignancies usually cluster in the zinc finger 1 (ZF1) and the ZF2 domains. Mutations in different locations of GATA2 may have distinct impact on clinico-biological features and outcomes in AML patients, but little is known in this aspect. In this study, we explored GATA2 mutations in 693 de novo non-M3 AML patients and identified 44 GATA2 mutations in 43 (6.2%) patients, including 31 in ZF1, 10 in ZF2, and three outside the two domains. Different from GATA2 ZF2 mutations, ZF1 mutations were closely associated with French-American-British (FAB) M1 subtype, CEBPA double mutations (CEBPAdouble-mut), but inversely correlated with FAB M4 subtype, NPM1 mutations, and FLT3-ITD. ZF1-mutated AML patients had a significantly longer overall survival (OS) than GATA2-wild patients and ZF2-mutated patients in total cohort as well as in those with intermediate-risk cytogenetics and normal karyotype. ZF1 mutations also predicted better disease-free survival and a trend of better OS in CEBPAdouble-mut patients. Sequential analysis showed GATA2 mutations could be acquired at relapse. In conclusion, GATA2 ZF1 mutations are associated with distinct clinico-biological features and predict better prognosis, different from ZF2 mutations, in AML patients.
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- 2018
9. Prognostic impacts and dynamic changes of cohesin complex gene mutations in de novo acute myeloid leukemia
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Chien-Ting Lin, Chien-Yuan Chen, Szu-Chun Hsu, Bor-Sheng Ko, Yu-Chiao Chiu, Wen-Chien Chou, Cheng-Hong Tsai, Tzung-Yi Lin, Mei-Hsuan Tseng, Chieh-Yu Liu, Liang-In Lin, Hsin-An Hou, Ming Yao, Ming-Chih Liu, Chi-Cheng Li, Chia-Wen Liu, Shang-Ju Wu, Woei Tsay, Shang-Yi Huang, Eric Y. Chuang, Yuan-Yeh Kuo, Hwei-Fang Tien, Jih-Luh Tang, and Chien-Chin Lin
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Male ,0301 basic medicine ,Myeloid ,Cohesin complex ,Chromosomal Proteins, Non-Histone ,DNA Mutational Analysis ,Cell Cycle Proteins ,Kaplan-Meier Estimate ,Gene mutation ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,Disease-Free Survival ,03 medical and health sciences ,Correspondence ,medicine ,Humans ,Proportional Hazards Models ,Mutation ,De novo acute ,Myeloid leukemia ,Hematology ,Prognosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Leukemia, Myeloid, Acute ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cancer research ,Female - Published
- 2017
10. Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome
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Xiu-Wen Liao, Mei-Hsuan Tseng, Yuan-Yeh Kuo, Ming Yao, Chia-Wen Liu, Yen-Ling Peng, Ming-Chih Liu, Hwei-Fang Tien, Cheng-Hong Tsai, Chieh-Yu Liu, Chien-Chin Lin, Wen-Chien Chou, Jih-Luh Tang, Hsin-An Hou, and Liang-In Lin
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0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Myeloid ,Adolescent ,Kaplan-Meier Estimate ,Gene mutation ,Lower risk ,IDH2 ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Gene ,Genetic Association Studies ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,Risk stratification ,Mutation ,Female ,business - Abstract
Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1, DNMT3A, and TP53 were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (P
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- 2018
11. Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish
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Hsieh Ms, Liang-In Lin, Jeng-Wei Lu, Hwei-Fang Tien, Chen Cy, and Hsin-An Hou
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0301 basic medicine ,medicine.medical_specialty ,NPM1 ,Myeloid ,Biology ,SOXC Transcription Factors ,Animals, Genetically Modified ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Animals ,Zebrafish ,Myelopoiesis ,Hematology ,Myeloid leukemia ,Zebrafish Proteins ,medicine.disease ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Haematopoiesis ,Leukemia ,Leukemia, Myeloid, Acute ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Original Article ,Bone marrow ,Nucleophosmin - Abstract
The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status. To elucidate the role of SOX4 in leukemogenesis, we generated a transgenic zebrafish model that overexpressed human SOX4 in the myeloid lineage Tg(spi1-SOX4-EGFP). These transgenic zebrafish showed, at 5 months of age, increased myelopoiesis with dedifferentiation in kidney marrow. At 9 months of age, their kidney structure was significantly effaced and distorted by increased infiltration of myeloid progenitor cells. These results suggest that SOX4 is not only an independent prognostic factor of AML, but also an important molecular factor in leukemogenesis.
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- 2017
12. Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia
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Yuan-Yeh Kuo, Chou Wc, Gong Z, Chunyu Liu, Hwei-Fang Tien, Jeng-Wei Lu, Ying-Chieh Chiang, Lin Ty, Jih-Luh Tang, Chien-Chin Lin, Mei-Hsuan Tseng, Cheng-Hong Tsai, Liang-In Lin, Hsin-An Hou, and Yen-Ling Peng
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Adult ,Male ,0301 basic medicine ,Myeloid ,Adolescent ,Biology ,medicine.disease_cause ,Disease-Free Survival ,Animals, Genetically Modified ,03 medical and health sciences ,Suppressor of Cytokine Signaling 1 Protein ,0302 clinical medicine ,hemic and lymphatic diseases ,CEBPA ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Zebrafish ,Aged ,Aged, 80 and over ,Suppressor of cytokine signaling 1 ,Myeloid leukemia ,Hematology ,Middle Aged ,Zebrafish Proteins ,medicine.disease ,Neoplasm Proteins ,Survival Rate ,Leukemia, Myeloid, Acute ,Leukemia ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Original Article ,Myelopoiesis ,Carcinogenesis ,Nucleophosmin - Abstract
Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Compared to patients with lower SOCS1 expression, those with higher expression had lower complete remission rates and shorter overall survival. Further, higher expression of SOCS1 in the BM was an independent unfavorable prognostic factor irrespective of age, white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the kidney or spleen structure were effaced and distorted, mimicking leukemia phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the leukemic process. The results indicate SOCS1 plays an important role in AML and its higher expression serves as a new biomarker to risk-stratify AML patients.
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- 2017
13. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
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Chia-Wen Liu, Chen Yc, Shang-Yi Huang, Hwei-Fang Tien, Chiang Yc, Yuan-Yeh Kuo, Hsin-An Hou, Ming Yao, Mei-Hsuan Tseng, Ming-Chih Liu, Wen-Chien Chou, Liu Cy, Chien-Ting Lin, Chien-Yuan Chen, Jih-Luh Tang, Liang-In Lin, Chi-Cheng Li, Woei Tsay, Szu-Chun Hsu, Bor-Sheng Ko, and Shang-Ju Wu
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Myeloid ,Adolescent ,Kaplan-Meier Estimate ,Gene mutation ,Young Adult ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Longitudinal Studies ,neoplasms ,Survival analysis ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Proportional hazards model ,Cytogenetics ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Mutation (genetic algorithm) ,Immunology ,Mutation ,Disease Progression ,Original Article ,Female ,Tumor Suppressor Protein p53 ,business ,Nucleophosmin ,Follow-Up Studies - Abstract
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
- Published
- 2015
14. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome
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Chien-Yuan Chen, Chen Tc, Woei Tsay, Ming Yao, Shang-Ju Wu, Chou Wc, Lai Yj, Hsin-An Hou, Chia-Wen Liu, Szu-Chun Hsu, Chen Yc, Bor-Sheng Ko, Liu Cy, Chiang Yc, Huang Cf, Lee Fy, Mei-Hsuan Tseng, Ming-Chih Liu, Jih-Luh Tang, Hwei-Fang Tien, Shang-Yi Huang, and Yuan-Yeh Kuo
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sequential analyses ,Neuroblastoma RAS viral oncogene homolog ,medicine.medical_specialty ,Hematology ,business.industry ,Gene mutation ,Trisomy 8 ,medicine.disease ,medicine.disease_cause ,ASXL1 mutation ,myelodysplastic syndrome ,Leukemia ,Oncology ,Internal medicine ,Mutation (genetic algorithm) ,medicine ,Cancer research ,Original Article ,prognosis ,KRAS ,business ,Gene - Abstract
Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.
- Published
- 2014
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