Search

Your search keyword '"Mayakonda, A"' showing total 693 results
Start Over Author "Mayakonda, A"
693 results on '"Mayakonda, A"'

52. Supplemental figure legends from Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma

Author

Sun, Haibo, primary, Lin, De-Chen, primary, Cao, Qi, primary, Pang, Brendan, primary, Gae, David D., primary, Lee, Victor Kwan Min, primary, Lim, Huey Jin, primary, Doan, Ngan, primary, Said, Jonathan W., primary, Gery, Sigal, primary, Chow, Marilynn, primary, Mayakonda, Anand, primary, Forscher, Charles, primary, Tyner, Jeffrey W., primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

53. Supplementary Fig 3 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

54. Supplementary Fig 1 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

55. Data from RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling

Author

Loh, Xin-Yi, primary, Sun, Qiao-Yang, primary, Ding, Ling-Wen, primary, Mayakonda, Anand, primary, Venkatachalam, Nachiyappan, primary, Yeo, Mei-Shi, primary, Silva, Tiago C., primary, Xiao, Jin-Fen, primary, Doan, Ngan B., primary, Said, Jonathan W., primary, Ran, Xue-Bin, primary, Zhou, Si-Qin, primary, Dakle, Pushkar, primary, Shyamsunder, Pavithra, primary, Koh, Angele Pei-Fern, primary, Huang, Ruby Yun-Ju, primary, Berman, Benjamin P., primary, Tan, Soo-Yong, primary, Yang, Henry, primary, Lin, De-Chen, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

56. Supplementary Figure legends from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

58. Supplementary Fig 4 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

59. Supplementary Figures from Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma

Author

Yuan, Jiang, primary, Jiang, Yan-Yi, primary, Mayakonda, Anand, primary, Huang, Moli, primary, Ding, Ling-Wen, primary, Lin, Han, primary, Yu, Fenggang, primary, Lu, Yanan, primary, Loh, Thomas Kwok Seng, primary, Chow, Marilynn, primary, Savage, Samantha, primary, Tyner, Jeffrey W., primary, Lin, De-Chen, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

60. Supplementary Fig 2 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

61. Supplementary Fig 5 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

62. Supplementary Tables from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

Ding, Ling-Wen, primary, Sun, Qiao-Yang, primary, Tan, Kar-Tong, primary, Chien, Wenwen, primary, Thippeswamy, Anand Mayakonda, primary, Eng Juh Yeoh, Allen, primary, Kawamata, Norihiko, primary, Nagata, Yasunobu, primary, Xiao, Jin-Fen, primary, Loh, Xin-Yi, primary, Lin, De-Chen, primary, Garg, Manoj, primary, Jiang, Yan-Yi, primary, Xu, Liang, primary, Lim, Su-Lin, primary, Liu, Li-Zhen, primary, Madan, Vikas, primary, Sanada, Masashi, primary, Fernández, Lucia Torres, primary, Preethi, Hema, primary, Lill, Michael, primary, Kantarjian, Hagop M., primary, Kornblau, Steven M., primary, Miyano, Satoru, primary, Liang, Der-Cherng, primary, Ogawa, Seishi, primary, Shih, Lee-Yung, primary, Yang, Henry, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

63. Supplementary Data from RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling

Author

Loh, Xin-Yi, primary, Sun, Qiao-Yang, primary, Ding, Ling-Wen, primary, Mayakonda, Anand, primary, Venkatachalam, Nachiyappan, primary, Yeo, Mei-Shi, primary, Silva, Tiago C., primary, Xiao, Jin-Fen, primary, Doan, Ngan B., primary, Said, Jonathan W., primary, Ran, Xue-Bin, primary, Zhou, Si-Qin, primary, Dakle, Pushkar, primary, Shyamsunder, Pavithra, primary, Koh, Angele Pei-Fern, primary, Huang, Ruby Yun-Ju, primary, Berman, Benjamin P., primary, Tan, Soo-Yong, primary, Yang, Henry, primary, Lin, De-Chen, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

66. Supplementary_table 1-6, 8-12 from Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma

Author

Yuan, Jiang, primary, Jiang, Yan-Yi, primary, Mayakonda, Anand, primary, Huang, Moli, primary, Ding, Ling-Wen, primary, Lin, Han, primary, Yu, Fenggang, primary, Lu, Yanan, primary, Loh, Thomas Kwok Seng, primary, Chow, Marilynn, primary, Savage, Samantha, primary, Tyner, Jeffrey W., primary, Lin, De-Chen, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

67. Supplemental Tables from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

Sun, Haibo, primary, Lin, De-Chen, primary, Cao, Qi, primary, Guo, Xiao, primary, Marijon, Helene, primary, Zhao, Zhiqiang, primary, Gery, Sigal, primary, Xu, Liang, primary, Yang, Henry, primary, Pang, Brendan, primary, Lee, Victor Kwan Min, primary, Lim, Huey Jin, primary, Doan, Ngan, primary, Said, Jonathan W., primary, Chu, Peiguo, primary, Mayakonda, Anand, primary, Thomas, Tom, primary, Forscher, Charles, primary, Baloglu, Erkan, primary, Shacham, Sharon, primary, Rajalingam, Raja, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

68. Supplemental Figures from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

Sun, Haibo, primary, Lin, De-Chen, primary, Cao, Qi, primary, Guo, Xiao, primary, Marijon, Helene, primary, Zhao, Zhiqiang, primary, Gery, Sigal, primary, Xu, Liang, primary, Yang, Henry, primary, Pang, Brendan, primary, Lee, Victor Kwan Min, primary, Lim, Huey Jin, primary, Doan, Ngan, primary, Said, Jonathan W., primary, Chu, Peiguo, primary, Mayakonda, Anand, primary, Thomas, Tom, primary, Forscher, Charles, primary, Baloglu, Erkan, primary, Shacham, Sharon, primary, Rajalingam, Raja, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

69. Supplemental Figure legends from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

Sun, Haibo, primary, Lin, De-Chen, primary, Cao, Qi, primary, Guo, Xiao, primary, Marijon, Helene, primary, Zhao, Zhiqiang, primary, Gery, Sigal, primary, Xu, Liang, primary, Yang, Henry, primary, Pang, Brendan, primary, Lee, Victor Kwan Min, primary, Lim, Huey Jin, primary, Doan, Ngan, primary, Said, Jonathan W., primary, Chu, Peiguo, primary, Mayakonda, Anand, primary, Thomas, Tom, primary, Forscher, Charles, primary, Baloglu, Erkan, primary, Shacham, Sharon, primary, Rajalingam, Raja, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

70. Data from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

Sun, Haibo, primary, Lin, De-Chen, primary, Cao, Qi, primary, Guo, Xiao, primary, Marijon, Helene, primary, Zhao, Zhiqiang, primary, Gery, Sigal, primary, Xu, Liang, primary, Yang, Henry, primary, Pang, Brendan, primary, Lee, Victor Kwan Min, primary, Lim, Huey Jin, primary, Doan, Ngan, primary, Said, Jonathan W., primary, Chu, Peiguo, primary, Mayakonda, Anand, primary, Thomas, Tom, primary, Forscher, Charles, primary, Baloglu, Erkan, primary, Shacham, Sharon, primary, Rajalingam, Raja, primary, and Koeffler, H. Phillip, primary

Published
2023
Full Text
View/download PDF

72. ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion

Author

Vikas Madan, Lin Han, Norimichi Hattori, Weoi Woon Teoh, Anand Mayakonda, Qiao-Yang Sun, Ling-Wen Ding, Hazimah Binte Mohd Nordin, Su Lin Lim, Pavithra Shyamsunder, Pushkar Dakle, Janani Sundaresan, Ngan B. Doan, Masashi Sanada, Aiko Sato-Otsubo, Manja Meggendorfer, Henry Yang, Jonathan W. Said, Seishi Ogawa, Torsten Haferlach, Der-Cherng Liang, Lee-Yung Shih, Tsuyoshi Nakamaki, Q. Tian Wang, and H. Phillip Koeffler

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Chromosomal translocation t(8;21)(q22;q22) which leads to the generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in approximately 10% of acute myelogenous leukemia (AML). To identify somatic mutations that co-operate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing of an Asian cohort at diagnosis and relapse. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in depth the role of ASXL2 in normal hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid hyperplasia, splenomegaly, extramedullary hematopoiesis, and poor reconstitution ability in transplantation models. Parallel analyses of young and >1-year old Asxl2-deficient mice revealed age-dependent perturbations affecting, not only myeloid and erythroid differentiation, but also maturation of lymphoid cells. Overall, these findings establish a critical role for ASXL2 in maintaining steady state hematopoiesis, and provide insights into how its loss primes the expansion of myeloid cells.

Published
2018
Full Text
View/download PDF

73. Data from Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma

Author

H. Phillip Koeffler, De-Chen Lin, Jeffrey W. Tyner, Samantha Savage, Marilynn Chow, Thomas Kwok Seng Loh, Yanan Lu, Fenggang Yu, Han Lin, Ling-Wen Ding, Moli Huang, Anand Mayakonda, Yan-Yi Jiang, and Jiang Yuan

Abstract

Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced antineoplastic activities both in vitro and in vivo. An integrative analysis using both whole-transcriptome sequencing and chromatin immunoprecipitation sequencing pinpointed oncogenic transcriptional amplification mediated by super-enhancers (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated networks identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2, and the long noncoding RNA TP53TG1. These transcripts were highly and specifically expressed in NPC and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK, and TEAD1) may help establish and maintain SE activity across the genome. Taken together, our data establish the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimens for this disease. Cancer Res; 77(23); 6614–26. ©2017 AACR.

Published
2023

74. Supplemental Figures from Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma

Author

H. Phillip Koeffler, Jeffrey W. Tyner, Charles Forscher, Anand Mayakonda, Marilynn Chow, Sigal Gery, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, David D. Gae, Brendan Pang, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Fig. S1. GSEA analysis revealed significant enrichment of gene associated with genomic unstable EWS phenotype (A), cell cycle (B) and NF-κB (C) in SYK knockdown cells, and gene associated with metastasis (D) in cells treated with the SYK inhibitor. Fig. S2. Representative IHC photos of p-SYK expression in TC71 control and shSYK cells. No Ab, no antibody control; NC, scramble shRNA control. Fig. S3. TC71 cells were treated with 4 μmol/L GS-9973 or PRT062607 for 48 h, and cell cycle distribution was analyzed by PI staining. Fig. S4. TC71 and SKES1 cells were infected with control (NC) or sh-MYC lentivirus for 72h, and c-MYC protein level was evaluated by immunoblotting assay. Fig. S5.Total nuclear RNA was immunoprecipitated by the antibody-coated beads (either nonspecific IgG or anti-EZH2 antibody), reverse-transcribed and the cDNA was further amplified by qRT-PCR. Bar graphs displayed the relative MALAT1 levels (Y-axis) in different groups. Protein lysates (input, IgG and anti-EZH2 antibodies) were immunoblotted and probed with anti- EZH2 antibody (lower panel). Data represent mean {plus minus} SD, n=3.

Published
2023

75. Supplementary Fig 5 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Supplementary Fig. 5. Kaplan-Meier analysis of the survival of patients with different mutations.

Published
2023

76. Supplementary Figure legends from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Legends for Supplementary Figures

Published
2023

78. Data from Genomic and Epigenomic Heterogeneity of Hepatocellular Carcinoma

Author

H. Phillip Koeffler, Dong Yin, Er-Wei Song, Benjamin P. Berman, Jie Wang, Ling-wen Ding, Xiaoping Liu, Lehang Lin, Pinbo Huang, Huy Q. Dinh, Anand Mayakonda, and De-Chen Lin

Abstract

Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 hepatocellular carcinoma cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions, that is, located on the “trunk” of the evolutionary tree. In addition, we found that variants within several drug targets such as KIT, SYK, and PIK3CA were mutated in a fully clonal manner, indicating their therapeutic potentials for hepatocellular carcinoma. Temporal dissection of mutational signatures suggested that mutagenic processes associated with exposure to aristolochic acid and aflatoxin might play a more important role in early, as opposed to late, stages of hepatocellular carcinoma development. Moreover, we observed extensive intratumoral epigenetic heterogeneity in hepatocellular carcinoma based on multiple independent analytical methods and showed that intratumoral methylation heterogeneity might play important roles in the biology of hepatocellular carcinoma cells. Our results also demonstrated prominent heterogeneity of intratumoral methylation even in a stable hepatocellular carcinoma genome. Together, these findings highlight widespread intratumoral heterogeneity at both the genomic and epigenomic levels in hepatocellular carcinoma and provide an important molecular foundation for better understanding the pathogenesis of this malignancy. Cancer Res; 77(9); 2255–65. ©2017 AACR.

Published
2023

80. Supplementary Figures from Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma

Author

H. Phillip Koeffler, De-Chen Lin, Jeffrey W. Tyner, Samantha Savage, Marilynn Chow, Thomas Kwok Seng Loh, Yanan Lu, Fenggang Yu, Han Lin, Ling-Wen Ding, Moli Huang, Anand Mayakonda, Yan-Yi Jiang, and Jiang Yuan

Abstract

Supplementary Figure 1. Distribution of putative targets of the top-ranked small molecules Supplementary Figure 2. CDK7 silencing significantly inhibited cells growth Supplementary Figure 3. Cell viability assay of C666-1 cells treated with THZ1 Supplementary Figure 4. Cell-cycle arrested at G2/M stage in C666-1 and HK1 cells treated with THZ1 Supplementary Figure 5. Cell viability (A) and apoptosis assay (B) showing the effects of THZ1 treatment in PNHNC Supplementary Figure 6. THZ1 potently suppressed xenografts growth and lung metastasis of NPC cells in NOD/SCID mice Supplementary Figure 7. THZ1 exhibited prominent anti-NPC activity in NOD/SCID mice Supplementary Figure 8. THZ1 inhibited RNAPII-mediated transcription in NPC Supplementary Figure 9. Representative SE-associated genes in NPC and PNHNC Supplementary Figure 10. Gene Ontology enrichment analysis of SE-associated genes in PNHNC cell

Published
2023

82. Data from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here, we report the use of next-generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment, and the p53/cell-cycle pathway. Unique recurrent mutational hotspots were observed in epigenetic regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3 (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene, while the epigenetic regulator ARID1A and transcription factor CTCF were functionally identified as potential tumor suppressors. Analysis of 28 diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary paths and uncovered the ordering of acquisition of mutations in these patients. This study provides a detailed mutational portrait of pediatric ALL and gives insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390–400. ©2016 AACR.

Published
2023

83. Data from RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling

Author

H. Phillip Koeffler, De-Chen Lin, Henry Yang, Soo-Yong Tan, Benjamin P. Berman, Ruby Yun-Ju Huang, Angele Pei-Fern Koh, Pavithra Shyamsunder, Pushkar Dakle, Si-Qin Zhou, Xue-Bin Ran, Jonathan W. Said, Ngan B. Doan, Jin-Fen Xiao, Tiago C. Silva, Mei-Shi Yeo, Nachiyappan Venkatachalam, Anand Mayakonda, Ling-Wen Ding, Qiao-Yang Sun, and Xin-Yi Loh

Abstract

ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved adenylate-uridylate–rich elements (ARE) located in 3′untranslated regions (UTR) to mediate mRNA decay. We hypothesized that ZFP36L1 is a negative regulator of a posttranscriptional hub involved in mRNA half-life regulation of cancer-related transcripts. Analysis of in silico data revealed that ZFP36L1 was significantly mutated, epigenetically silenced, and downregulated in a variety of cancers. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo, whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wild-type and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells {plus minus} tet-on ZFP36L1 was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1. These targets included a number of key oncogenic transcripts such as HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3′UTRs of these targets for mRNA degradation, thus suppressing their expression. Dual luciferase reporter assays and RNA electrophoretic mobility shift assays showed that wild-type, but not zinc-finger mutant ZFP36L1, bound to HIF1A 3′UTR and mediated HIF1A mRNA degradation, leading to reduced expression of HIF1A and its downstream targets. Collectively, our findings reveal an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell-cycle progression.Significance:RNA-binding protein ZFP36L1 functions as a tumor suppressor by regulating the mRNA stability of a number of mRNAs involved in hypoxia and cell-cycle signaling.

Published
2023

84. Supplementary Fig 4 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Supplementary Fig. 4. p53 pathway is dysregulated in ALL.

Published
2023

85. Supplementary Fig 2 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Supplementary Fig. 2. Mutations found in the ASXL family of genes.

Published
2023

86. Data from Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma

Author

H. Phillip Koeffler, Jeffrey W. Tyner, Charles Forscher, Anand Mayakonda, Marilynn Chow, Sigal Gery, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, David D. Gae, Brendan Pang, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Purpose: Ewing sarcoma (EWS) is a devastating soft tissue sarcoma affecting predominantly young individuals. Tyrosine kinases (TK) and associated pathways are continuously activated in many malignancies, including EWS; these enzymes provide candidate therapeutic targets.Experimental Design: Two high-throughput screens (a siRNA library and a small-molecule inhibitor library) were performed in EWS cells to establish candidate targets. Spleen tyrosine kinase (SYK) phosphorylation was assessed in EWS patients and cell lines. SYK was inhibited by a variety of genetic and pharmacological approaches, and SYK-regulated pathways were investigated by cDNA microarrays. The transcriptional regulation of MALAT1 was examined by ChIP-qPCR, luciferase reporter, and qRT-PCR assays.Results: SYK was identified as a candidate actionable target through both high-throughput screens. SYK was highly phosphorylated in the majority of EWS cells, and SYK inhibition by a variety of genetic and pharmacologic approaches markedly inhibited EWS cells both in vitro and in vivo. Ectopic expression of SYK rescued the cytotoxicity triggered by SYK-depletion associated with the reactivation of both AKT and c-MYC. A long noncoding RNA, MALAT1, was identified to be dependent on SYK-mediated signaling. Moreover, c-MYC, a SYK-promoted gene, bound to the promoter of MALAT1 and transcriptionally activated MALAT1, which further promoted the proliferation of EWS cells.Conclusions: This study identifies a novel signaling involving SYK/c-MYC/MALAT1 as a promising therapeutic target for the treatment of EWS. Clin Cancer Res; 23(15); 4376–87. ©2017 AACR.

Published
2023

88. Supplementary Fig 1 from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Supplementary Fig. 1. Mutational spectrum of pediatric ALL.

Published
2023

92. Supplemental Tables S1-S9 from Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma

Author

H. Phillip Koeffler, Jeffrey W. Tyner, Charles Forscher, Anand Mayakonda, Marilynn Chow, Sigal Gery, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, David D. Gae, Brendan Pang, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Table S1. Small molecule inhibitors. Listing of all 116 agents on the screening inhibitor panel with respective molecular targets and sources Table S2. Primers for QRT-PCR and plasmid construction. Table S3. IC50s of 116 small molecule inhibitors in EWS cells. Table S4. IC50s of small molecule inhibitors in other cancer types. Table S5. Patients clinical information and H-score numbers. Table S6. MALAT1 expression among different cancer types ( patient sample tissues from Baird Sarcoma database). Table S6. Overlaps of lists of genes significantly co-downregulated and co-upregulated by SYK inhibitor GS-9973 (SYK i) and SYK knockdown (shSYK) in TC71 cells. Table S7. MALAT1 expression among different cancer types (patient sample tissues from Baird Sarcoma database). Table S8. MALAT1 Expression among different cancer types ( cancer cell lines from CCLE database). Table S9. ChIP-seq data source information.

Published
2023

93. Supplementary Tables from Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

Author

H. Phillip Koeffler, Henry Yang, Lee-Yung Shih, Seishi Ogawa, Der-Cherng Liang, Satoru Miyano, Steven M. Kornblau, Hagop M. Kantarjian, Michael Lill, Hema Preethi, Lucia Torres Fernández, Masashi Sanada, Vikas Madan, Li-Zhen Liu, Su-Lin Lim, Liang Xu, Yan-Yi Jiang, Manoj Garg, De-Chen Lin, Xin-Yi Loh, Jin-Fen Xiao, Yasunobu Nagata, Norihiko Kawamata, Allen Eng Juh Yeoh, Anand Mayakonda Thippeswamy, Wenwen Chien, Kar-Tong Tan, Qiao-Yang Sun, and Ling-Wen Ding

Abstract

Supplementary Table 1. Samples used for whole exome and targeted sequencing. Supplementary Table 2. Clinical information of patients. Supplementary Table 3. 560 Genes screened in the targeted sequencing. Supplementary Table 4. Sequences of shRNA or CRISPR-Cas9 sgRNA used in this study. Supplementary Table 5. Sequences of real-time PCR primers used in this study. Supplementary Table 6. Sequences of primers used for Sanger validation of CRISPR-Cas9 indel. Supplementary Table 7. Mutations of KRAS identified in this study have been found in a variety of cancers. Supplementary Table 8. Mutations of PTPN11 in other cancers occurring in the same location as in our ALL cohort. Supplementary Table 9. Recurrent mutation sites of FLT3 in different cancers. Supplementary Table 10. Cell lines or cancer samples harboring either E1099K or T1150A hotspot mutation of WHSC1. Supplementary Table 11. R1446 mutations of CREBBP recurrently occurred in a variety of cancers. Supplementary Table 12. Mutational hotspot (D1399) of EP300 occurring in other cancers occurring in the same location as in our ALL cohort.Supplementary Table 13. Rare mutations occurring in our ALL cohort (mutated in one individual each), but these mutations have been recurrently documented in the COSMIC cancer mutations database. Supplementary Table 14. Mutations of genes involved in DNA repair pathway in relapse samples.

Published
2023

94. Supplementary Data from RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling

Author

H. Phillip Koeffler, De-Chen Lin, Henry Yang, Soo-Yong Tan, Benjamin P. Berman, Ruby Yun-Ju Huang, Angele Pei-Fern Koh, Pavithra Shyamsunder, Pushkar Dakle, Si-Qin Zhou, Xue-Bin Ran, Jonathan W. Said, Ngan B. Doan, Jin-Fen Xiao, Tiago C. Silva, Mei-Shi Yeo, Nachiyappan Venkatachalam, Anand Mayakonda, Ling-Wen Ding, Qiao-Yang Sun, and Xin-Yi Loh

Abstract

ZFP36L1 is significantly downregulated and methylated in breast and bladder cancer, and inhibits cell cycle progression and hypoxia/HIF1A signaling.

Published
2023

95. Data from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

H. Phillip Koeffler, Raja Rajalingam, Sharon Shacham, Erkan Baloglu, Charles Forscher, Tom Thomas, Anand Mayakonda, Peiguo Chu, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, Brendan Pang, Henry Yang, Liang Xu, Sigal Gery, Zhiqiang Zhao, Helene Marijon, Xiao Guo, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Ewing sarcoma (EWS) is an aggressive bone malignancy that mainly affects children and young adults. The mechanisms by which EWS (EWSR1) fusion genes drive the disease are not fully understood. CRM1 (XPO1) traffics proteins from the nucleus, including tumor suppressors and growth factors, and is overexpressed in many cancers. A small-molecule inhibitor of CRM1, KPT-330, has shown therapeutic promise, but has yet to be investigated in the context of EWS. In this study, we demonstrate that CRM1 is also highly expressed in EWS. shRNA-mediated or pharmacologic inhibition of CRM1 in EWS cells dramatically decreased cell growth while inducing apoptosis, cell-cycle arrest, and protein expression alterations to several cancer-related factors. Interestingly, silencing of CRM1 markedly reduced EWS–FLI1 fusion protein expression at the posttranscriptional level and upregulated the expression of the well-established EWS-FLI1 target gene, insulin-like growth factor binding protein 3 (IGFBP3), which inhibits IGF-1. Accordingly, KPT-330 treatment attenuated IGF-1–induced activation of the IGF-1R/AKT pathway. Furthermore, knockdown of IGFBP3 increased cell growth and rescued the inhibitory effects on IGF-1 signaling triggered by CRM1 inhibition. Finally, treatment of EWS cells with a combination of KPT-330 and the IGF-1R inhibitor, linsitinib, synergistically decreased cell proliferation both in vitro and in vivo. Taken together, these findings provide a strong rationale for investigating the efficacy of combinatorial inhibition of CRM1 and IGF-1R for the treatment of EWS. Cancer Res; 76(9); 2687–97. ©2016 AACR.

Published
2023

96. Supplemental Figure legends from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

H. Phillip Koeffler, Raja Rajalingam, Sharon Shacham, Erkan Baloglu, Charles Forscher, Tom Thomas, Anand Mayakonda, Peiguo Chu, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, Brendan Pang, Henry Yang, Liang Xu, Sigal Gery, Zhiqiang Zhao, Helene Marijon, Xiao Guo, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Figure legends for supplemental figures S1-S6.

Published
2023

97. Supplemental Tables from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

H. Phillip Koeffler, Raja Rajalingam, Sharon Shacham, Erkan Baloglu, Charles Forscher, Tom Thomas, Anand Mayakonda, Peiguo Chu, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, Brendan Pang, Henry Yang, Liang Xu, Sigal Gery, Zhiqiang Zhao, Helene Marijon, Xiao Guo, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Table S1. qRT-PCR primers. Table S2. CRM1 expression among different cancer types patient sample tissues. Table S3. CRM1 Expression among different cancer types ( cancer cell lines from CCLE database). Table S4. patients clinical infomation and h score sorting. Table S5. Overlaps of lists of genes in EW8 and SKES1 under treatment with KPT-330. Table S6. Overlaps of lists of genes by KPT-330 and EWS-FLI1 regulation.

Published
2023

98. Supplemental Figures from CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1–Dependent IGF-1 Signaling

Author

H. Phillip Koeffler, Raja Rajalingam, Sharon Shacham, Erkan Baloglu, Charles Forscher, Tom Thomas, Anand Mayakonda, Peiguo Chu, Jonathan W. Said, Ngan Doan, Huey Jin Lim, Victor Kwan Min Lee, Brendan Pang, Henry Yang, Liang Xu, Sigal Gery, Zhiqiang Zhao, Helene Marijon, Xiao Guo, Qi Cao, De-Chen Lin, and Haibo Sun

Abstract

Fig. S1. Expression of CRM1 in EWS cell lines. Fig. S2. Treatment of KPT-330 caused tolerable cytotoxic effect in normal CD34+ cells. Fig. S3.p53 is regulated to drive KPT-330 dependent anti-proliferation effect in wildtype EWS cell lines. Fig. S4. KPT-330 has modest effect on regulation of other fusion proteins. Fig. S5. Combination of KPT-330 and Crizotinib synergistically inhibited cell proliferation in EWS cell lines. Fig. S6. Venn diagram of genes co-downregulated by KPT-330 compared with genes downregulated by EWS-FLI1.

Published
2023

99. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse

Author

Garg, Manoj, Nagata, Yasunobu, Kanojia, Deepika, Mayakonda, Anand, Yoshida, Kenichi, Haridas Keloth, Sreya, Zang, Zhi Jiang, Okuno, Yusuke, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Miyano, Satoru, Ding, Ling-Wen, Alpermann, Tamara, Sun, Qiao-Yang, Lin, De-Chen, Chien, Wenwen, Madan, Vikas, Liu, Li-Zhen, Tan, Kar-Tong, Sampath, Abhishek, Venkatesan, Subhashree, Inokuchi, Koiti, Wakita, Satoshi, Yamaguchi, Hiroki, Chng, Wee Joo, Kham, Shirley-Kow Yin, Yeoh, Allen Eng-Juh, Sanada, Masashi, Schiller, Joanna, Kreuzer, Karl-Anton, Kornblau, Steven M., Kantarjian, Hagop M., Haferlach, Torsten, Lill, Michael, Kuo, Ming-Chung, Shih, Lee-Yung, Blau, Igor-Wolfgang, Blau, Olga, Yang, Henry, Ogawa, Seishi, and Koeffler, H. Phillip

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results