To date, transforming ability of the activating mutations of JAK3 (such as P132T, L156P, R172Q, E183G, Q501H, M511I, A572V, A573V, R657Q, and V722I) has been previously validated in Ba/F3 cells (8, 12, 19, 20). By continuing to use Gov.sg, you accept our use of cookies. Poon, W.S. Lim, Study supervision: S. Rozen, B.T. The JAK3, JAK1, JAK2, and TYK2 mutation status in these samples was confirmed by Sanger sequencing of all coding exons. Thus, it is conceivable that the JAK3 mutation may play an important role in the pathogenesis of NKTCLs. and was admitted to the Singapore Bar in 1978. See more people named Choonkiat Gan. Gan Teng (Reno) Gan Teng. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs. The JAK family of tyrosine kinases comprises 4 members: JAK1, JAK2, JAK3, and TYK2. Our findings have important implications for the management of patients with NKTCLs. Teh, S.T. Ng, V. Rajasegaran, S. Rozen, B.T. Experiments were repeated at least 3 times.y. There is thus an urgent need to identify novel genetic aberrations and potential treatment targets in NKTCLs. 3B). There has been little progress in basic science and clinical research in this subtype of lymphoma, which continues to constitute a major challenge in managing these patients as there is currently no accepted standard first-line treatment for NKTCLs. We compared our variants against the common polymorphisms present in dbSNP 131 and in the 1000 genomes databases to discard any common SNPs. A, the NK-S1 cells harboring JAK3A572V were able to grow in an IL-2–independent manner. JAK3 siRNA or control siRNA (Dharmacon) were transfected into NK-S1 cell line using RNAiMAX (Invitrogen) according to the manufacturer’s protocols. We conducted whole-exome sequencing and identified Janus kinase 3 ( JAK3 ) somatic–activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Allen, W.S. Identification and characterization of JAK3-activating mutations. Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation by IL-2, Activating alleles of JAK3 in acute megakaryoblastic leukemia, Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency, Somatically acquired JAK1 mutations in adult acute lympho-blastic leukemia, Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down’s syndrome, FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma, Jak3- and JNK-dependent vascular endothelial growth factor expression in cutaneous T-cell lymphoma, Activation status of the JAK/STAT3 pathway in mantle cell lymphoma, JAK3 mutations occur in acute megakaryoblastic leukemia both in Down syndrome children and non-Down syndrome adults, A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera, Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers, Somatic mutations affect key pathways in lung adenocarcinoma, Activating mutations in human acute megakaryoblastic leukemia, Array-based genomic resequencing of human leukemia, Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models, The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation, CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP, The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications, KRAS mutation detection in paired frozen and formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues, An Epstein-Barr virus positive natural killer lymphoma xenograft derived for drug testing, A novel natural killer cell line (KHYG-1) from a patient with aggressive natural killer cell leukemia carrying a p53 point mutation, Lung Microbiome and Lung Cancer Prognosis, Pan-Cancer Analysis of HLA LOH as a Method of Immune Evasion, Cancer Epidemiology, Biomarkers & Prevention, Disclosure of Potential Conflicts of Interest. Gan Choon Kiat, deputy director of the LTA's corporate transformation office, was quoted by Channel NewsAsia as saying that more themed trains will be rolled out in future. Commuters can also grab the Christmas tree-shaped cards hanging from the handrails to use as greeting cards. ISSN: 2159-8274, Sign In to Email Alerts with your Email Address. Janus Kinase 3–Activating Mutations Identified in Natural Killer/T-cell Lymphoma, Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009, Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years, International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes, P53, N- and K-Ras, and beta-catenin gene mutations and prognostic factors in nasal NK/T-cell lymphoma from Hokkaido, Japan. This study is dedicated to Dr. Han Mo Koo. For Sanger sequencing, PCR was carried out with Platinum Taq Polymerase (Life Technologies, catalog number 10966-083) and cycled at 95°C for 10 minutes; 39 cycles of 95°C for 30 seconds; 60°C for 30 seconds, 72°C for 1 minute, and a final extension of 72°C for 10 minutes. Join Facebook to connect with Choon Kiat Gan and others you may know. Lee, L.C. Gan Choon Beng has been a GBN Mentor since 2008 and has worked with many mentees in various areas of business. Whole-exome sequencing was successfully conducted on fresh-frozen NKTCLs and paired blood samples from 4 different patients. ©2012 AACR. Cancer Discovery Natural killer (NK) cells as a responder to interleukin 2 (IL 2). MIGR1 expression vectors containing full-length wild-type JAK3 or JAK3A572V mutant were generously provided by Dr. Brian Druker (Howard Hughes Medical Institute, Chevy Chase, MD; ref. See the complete profile on LinkedIn and discover Gan’s connections and jobs at similar companies. Domain structure of JAK3 (bottom) and the positions of JAK3A572V(c.1715C>T) and JAK3A573V (c.1718C>T; top) identified through Sanger sequencing of NKTCL samples. Gan Choon Beng is a practicing lawyer and is the Senior Director at Infinitus Law Corporation and head of its Corporate, Commercial and Technology Department.He graduated from the University of Singapore (now known as the National University of Singapore) in 1977 with an LLB (Hons.) Experiments were repeated at least 3 times. The coding exons of JAK3 were fully sequenced in these 3 cell lines, and we confirmed that only NK-S1 harbored a homozygous JAK3A572V mutation. To decline cookies at any time, you may adjust your browser settings. The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. Furthermore, Annexin V staining revealed that the reduction of NK-S1 viability was due to an increase in cellular apoptosis (Fig. JAK1 and JAK3 mediate IL-2 receptor signaling through phosphorylation of STAT transcription factors (7). CP-690550, a novel pan-JAK inhibitor, has recently been shown to inhibit adult TCL/leukemia (ATLL) cells (22) and ATLL xenograft tumors and is currently in phase III trials for the treatment of rheumatoid arthritis (23). View Gan Chin Kiat’s profile on LinkedIn, the world’s largest professional community. Gan Xa. For FFPE samples, genomic DNA was extracted from one or two 10-μm slices from each sample by removal of paraffin followed by proteinase K digestion according to standard procedures. eISSN: 2159-8290 In contrast, JAK3 wild-type KHYG-1 cells were clearly IL-2–dependent (Fig. He currently oversees The GBN Mentoring Program together with Seow Kiat Wang.. C, drug-induced apoptosis was evaluated by Annexin V-FITC (fluorescein isothiocyanate) staining, followed by flow cytometric analysis. *, P < 0.05 compared with vehicle control (vehicle). Choon Kiat Chen Solutions Director , China Mobile International Choon Kiat has more than 25 years in the Telco/ICT industry since attaining his degree in Computing Science(1994) and MBA(2000). The primer sequences used for validation are listed in Supplementary Table S4. Effects of CP-690550 on NKTCL cell lines. Subsequently, he was also appointed the Chief Executive Officer and Director of ComfortDelGro Bus Pte Ltd. View the profiles of people named Kiat Gan. Land Transport Authority (LTA) Singapore is a entity based in 1 Hampshire Road, Singapore, 219428, Singapore, which employs 908 executives. S. Rozen is employed by Duke University as Associate Professor Track V. No potential conflicts of interests were disclosed by the other authors. Koo, S.Y. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. Choon Kiat Gan. Interleukin (IL)-2 is an essential cytokine required for the proliferation and activation of NK cells (6). DNA of frozen tissue and paired blood samples was isolated using a DNeasy blood and tissue mini kit and a QIAmp DNA blood midi kit (Qiagen), respectively, according to the manufacturer’s instruction. Reciprocally, KHYG-1 cells transiently overexpressing a mutated JAK3 (JAK3A572V) cDNA showed IL-2–independent proliferation and autophosphorylation of JAK3 and STAT5 (Fig. This is the first time that the Land Transport Authority (LTA) has introduced a festive-themed train. To decline cookies at any time, you may adjust your browser settings. We retained SNVs that passed additional quality filters (a quality by depth ≥5, a variant depth ≥5, a normal depth ≥5) and discarded any SNV close to a micro-indel or to several other SNVs. Contact Information. The JAK/STAT pathway is a key component in normal hematopoiesis. The train is decked with yuletide artwork including Santa hats and reindeer antlers on the windows which serve as photo opportunities, Channel NewsAsia reported. We use cookies to tailor your browsing experience. The extent of drug-induced apoptosis was evaluated by Annexin V-FITC (BD Biosciences) staining. D, phosphorylation of JAK3 and STAT5 in KHYG-1 cells were IL-2–dependent. The train, which will run till Dec 27, was launched at Ang Mo Kio station by Transport Minister Khaw Boon Wan, who rode it to Marina Bay station with nine students from Pathlight School. Cells were seeded at 2 × 104 cells/100 μL/well in 96-well plates and treated with or without CP-690550 (Selleck Chemical, S5001) at various concentrations before being subjected to MTS assay (Promega). Ng, V. Rajasegaran, H.L. 3A). The JAK3A572V and JAK3A573V mutations found in our samples were located at the JH2 pseudokinase domain that is known to have an autoinhibitory effect on the JH1 kinase domain. Natural killer/T-cell lymphoma (NKTCL) is particularly prevalent in Asian countries and some parts of Latin America. B, KHYG-1 cells were transiently transfected with wild-type JAK3 (JAK3 WT) or mutated JAK3 expression vectors (i.e., JAK3A572V). Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. We offer the most extensive selection of academic programmes in Singapore, collaborating with leading universities worldwide to provide our students with diverse opportunities for overseas exposure. He is also on the board of 11 other companies. As such, it is possible that the number of homozygous tumors reported is actually an underestimate and that this value should be regarded as a lower limit. 8). The relative p-JAK3, p-STAT5, JAK3, and STAT5 levels in these cells were detected by Western blotting (top), and proliferation assays using these cells were conducted for 48 hours with or without IL-2 (bottom). Mr Gan Khai Choon (iii) Mr Hoh Weng Ming (iv) Mr Tan Aik-Leang (v) Mr Neo Poh Kiat (vi) Mr Yan Ping (vii) Mr Han Yi Yong (viii) Mr Raymond … This latter difference was not statistically significant (Supplementary Table S3). Ong, K.-W. Yeoh, K.A. Transient overexpression of these 2 constructs in KHGY-1 cells was then generated using Effectene Transfection Reagent (Qiagen Inc.). Join Facebook to connect with Kiat Gan and others you may know. Poon, G.E. Gan Teng. Artnexus Design is the appointed creative agency for the NDP 2013 publicity production. A, NK-S1, KHYG-1, and K562 cells were treated with CP-690550 for 48 hours, and the effect on STAT5 phosphorylation was evaluated by Western blotting. Sino Group is one of the leading property developers in Hong Kong. Cogan Gan. View Ang Choon Kiat Amos’ profile on LinkedIn, the world’s largest professional community. Koo, S.Y. Lim, Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): G.C. The resulting products were run on an ABI 3730 DNA analyzer. FFPE tissue blocks from 61 patients with NKTCLs were procured for mutation analysis. KHYG-1 was obtained from the Japanese Collection of Research BioResources (28) and cultured in RPMI medium (Life Technologies) supplemented with heat-inactivated FBS (10%), equine serum (10%), and 200 IU/mL of recombinant human IL-2 (Novartis). Mr Gan Juay Kiat was appointed Chief Executive Officer of SBS Transit Ltd on 1 March 2010. Koo, S.Y. Teh, S.T. In summary, our studies identified, for the first time, frequent JAK3 mutations in NKTCLs. Choon Kiat Gan नाम के लोगों की प्रोफ़ाइल देखें. Gan. In total, we found mutations in JAK3 in 23 of 65 (35.4%) cases (Supplementary Table S3) and for JAK1, besides the case with concomitant JAK1Y652D and JAK3A572V mutations described above, no additional mutations were identified. Koo, K.-W. Yeoh, C.C.Y. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Gan Ja. Ng, V. Rajasegaran, H.L. Lim, Development of methodology: G.C. They also indicated that targeting the JAK/STAT pathway in this disease is a potentially effective therapeutic approach that warrants further investigation. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic–activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Thank you for sharing this Cancer Discovery article. Tan, S.L. Teh, S.T. Tan, T. Tang, S.L. If you don’t like our faces, listen to our fortnightly podcast E-Junkies where we lepak one corner with famous people, Your daily good stuff - AsiaOne stories delivered straight to your inbox, AsiaOne Online Pte Ltd. Company Registration No. Lim, Supplied pathologic diagnosis for case series: L. Tan. Signals were visualized with enhanced chemiluminescence (ECL; Amersham). After blocking, membranes were probed with primary antibodies against phospho-STAT5 (Cell Signaling, catalog number 9356), STAT5 (Cell Signaling, catalog number 9363), phospho-JAK3 (Cell Signaling, catalog number 5031), JAK3 (Cell Signaling, catalog number 3775), and β-actin followed by either peroxidase-conjugated anti-mouse or anti-rabbit secondary antibody. 1). Acquisition of the data were conducted on FACSCalibur flow cytometer (BD Biosciences). By continuing to use Gov.sg, you accept our use of cookies. In this study, we conducted whole-exome sequencing to identify somatic mutations in protein-coding genes of NKTCL tumors to shed light on their pathogenesis and to uncover potential new therapeutic targets, which are urgently needed. Gan has 3 jobs listed on their profile. However, this phenomenon was not observed in the K562 cells in which STAT5 phosphorylation is dependent on BCR/ABL1 (8) and not JAK3 (Fig. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Ong, S. Rozen, P. Tan, B.T. Only SNVs in exons or in canonical splice sites were further analyzed. One tumor harbored both JAK1Y652D and JAK3A572V mutations, whereas the other tumor harbored a JAK3A573V mutation. We used Burrows Wheeler Aligner to align the sequence reads to the human reference genome NCBI built 37.1 (hg19) and then we ran SamTools to remove PCR duplicates. Importantly, NK-S1 cells treated with JAK3 siRNAs exhibited a significant reduction in cell proliferation and also decreased autophosphorylation of JAK3 and STAT5, compared with cells treated with control siRNAs (Fig. The cycling and melting conditions were as follows: 1 cycle of 98°C for 2 minutes; 39 cycles of 98°C for 5 minutes; 58°C for 10 minutes; 1 cycle of 95°C for 30 minutes; and a melt from 72°C to 95°C increasing at 0.2°C/s. Welcome to Singapore's directory of Specialist Doctors and Surgeons in private practice. With specialists from across all medical and surgical fields conveniently located islandwide, SingaporeDoc will help you find the right specialist. 2A) and constitutive phosphorylation of both JAK3 and STAT5 (Fig. Ng, C.K. Our pipeline first recalibrates the base qualities and realigns the sequence reads around micro-indels. Currently, Choon Kiat Tan occupies the position of Group Financial Controller at SUTL Enterprise Ltd. Mr. Tan is also Member of Institute of Singapore Chartered Accountants. Choon kiat menyenaraikan 6 pekerjaan pada profil mereka. HRM difference curves deviating from the wild-type curve were considered to be harboring a mutation. Find contact's direct phone number, email address, work history, and more. These are some of the notable cases which SPD officers handled in 2011: In PP v Abdul Razak Bin Hamid and PP v Tan Chye Guan Martin, the accused persons were both heinous child molesters, dubbed the “Letterbox Molester” and “Heartbeat Molester” respectively.They engaged in ruses to con children into physical contact and committed the offences over 20 years and 11 years respectively. Facebook gives people the power to share and makes the world more open and connected. 4B). Others With a Similar Name. In accordance, transiently overexpressing a JAK3A572V in a JAK3 wild-type NKTCL cell line (KHYG-1) resulted in IL-2–independent cell proliferation and the activation of JAK/STAT signaling pathways. Consistent with the high frequency of JAK3 mutations (35%) in NKTCLs, use of CP-690550 in the JAK3-mutant NKTCL cell line showed inhibition in the phosphorylation of STAT5 along with reduced cell viability. Lim, Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc. All 3 missense mutations were predicted by PolyPhen to be damaging (5). A research-intensive university with an entrepreneurial dimension, NUS is ranked consistently as one of the world's top universities. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt … Lim, Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S.L. Presently, Khai Choon Gan occupies the position of Non-Independent Non-Executive Chairman for HL Global Enterprises Ltd., Non-Executive Chairman of Beijing Fortune Hotel Co., Ltd. and Managing Director at Hong Leong International (Hong Kong) Ltd. This study was approved by the SingHealth Centralized Institutional Review Board (CIRB), study number 2004/407/B. 4C). Lim, Writing, review, and/or revision of the manuscript: G.C. B, NK-S1 cell lysates were harvested for Western blotting, and the results showed that phosphorylation of JAK3 and STAT5 are IL-2–independent. NK-S1, established from a previously described NKTCL xenograft (27), was cultured in Dulbecco’s Modified Eagle’s Medium (DMEM; Life Technologies) supplemented with 10% heat-inactivated FBS and 10% equine serum. Gan Choon Kiat, deputy director of the LTA's corporate transformation office, was quoted by Channel NewsAsia as saying that more themed trains will be rolled out in future. Captured DNA libraries were sequenced with the Illumina GAIIx Genome Analyzer, yielding 150 (2 × 75) base pairs from the final library fragments. Yap, K.A. Lihat profil Choon kiat Gan di LinkedIn, komuniti profesional yang terbesar di dunia. Matched fresh-frozen tissue and peripheral blood samples were obtained from 4 consented patients with NKTCLs for whole-exome sequencing. Total proteins were extracted with lysis buffer, resolved by SDS-PAGE gels, and blotted onto a nitrocellulose membrane. Significance: Gene mutations causing NKTCL have not been fully identified. The presence of nonmalignant stroma (our samples contained at least 50% tumor content) or tumor subclones makes it difficult to assess whether these “heterozygous” tumors might actually represent a mixture of JAK3 homozygous–mutated cancer cells admixed with normal tissue. Lee, I. Cutcutache, W. Yu, C.C.Y. Ang Choon Kiat has 4 jobs listed on their profile. The report said Gan, 61, was taking responsibility for an “inappropriate relationship”. Cellular studies revealed that the NK-S1 cells harboring the homozygous JAK3A572V mutation are able to proliferate in cell culture without IL-2 stimulation, with constitutive expression of both phosphorylated JAK3 and STAT5. Among the patients with JAK3 mutations, there were 17 heterozygous JAK3A572V, 2 homozygous JAK3A572V, 2 heterozygous JAK3A573V, 1 homozygous JAK3A573V, and 1 heterozygous with both JAK3A572V and JAK3A573V mutations. Ang Choon Kiat has 8 jobs listed on their profile. These data are compelling and suggest a potential target for this otherwise fatal disease. In line with the functional importance of the activating JAK3 mutations identified, we tested whether JAK3 mutations could confer IL-2–independent growth to the NKTCL cell line (NK-S1) that harbors a homozygous JAK3A572V mutation. I. Proliferative response and establishment of cloned cells. Among these 4 members, JAK3 signaling is specifically related to T-cell development and proliferation (8) with loss-of-function mutations resulting in severe combined immunodeficiency characterized by the lack of T and NK cells (9). Besides hematologic neoplasia, nonhematologic cancers, including breast, stomach, and lung cancer, have also been found to harbor JAK3 mutations (17, 18). View Ang Choon Kiat Amos’ profile on LinkedIn, the world's largest professional community. We also conducted Epstein-Barr virus–encoded RNA (EBER) testing on all cases. IL-2–independent growth and constitutive JAK3 and STAT5 phosphorylation in a JAK3A572V-mutant NKTCL cell line. Gan Chimeg. JAK3A572V mutation causes constitutive JAK3 activity and IL-2–independent proliferation of NKTCL cells. View Choon Chia's business profile as Infrastructure & Operation Director, Systems (Rail Asset O&M) at Land Transport Authority. Koo, S.Y. Enter multiple addresses on separate lines or separate them with commas. Copyright © 2021 by the American Association for Cancer Research. Lihat profil lengkap di LinkedIn dan terokai kenalan dan pekerjaan Choon kiat di syarikat yang serupa. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. The men's 1000 metres competition at the 2010 Asian Games in Guangzhou was held on 18 November 2010 at the Zengcheng Dragon Boat Lake. Despite multiagent chemotherapy and involved-field radiotherapy, the 5-year overall survival rate is approximately 9% for non-nasal NKTCLs and 42% for nasal NKTCLs (2, 3). In parallel, these cells were harvested, and protein extracts were subjected to Western blotting with antibodies against phosphorylated JAK3 (p-JAK3), phosphorylated STAT5 (p-STAT5), JAK3, STAT5, or β-actin as a normalization control. The JAK3A572V and JAK3A573V mutations were located at exon 12, in the Janus homology domain 2 (JH2) that negatively regulates the Janus homology domain 1 (JH1) kinase activity (Fig. Mr Gan first joined ComfortDelGro Corporation Limited as Group Corporate Planning Officer in February 2006. We do not retain these email addresses. We use cookies to tailor your browsing experience. The next step uses a GATK Unified Genotyper that does the consensus calling to identify SNVs. Heng, A. Gan, S.T. Ong, P. Tan, B.T. To detect single-nucleotide variants (SNV), we used a discovery pipeline based on the Genome Analyzer Toolkit (GATK). NK-S1 (JAK3A572V homozygous mutant) and KHYG-1 (wild-type JAK3) cells were cultured with or without recombinant human IL-2 up to 7 days and followed by MTS assay. The single EBER-negative case was a cutaneous deposit taken from a patient with EBER+ nasal NKTCLs (Supplementary Table S3). 2B). JAK-mutant (NK-S1) cells showed IL-2–independent growth (Fig. It accounts for up to half of all mature TCL cases in Asia (1). View Yuen Kin Pheng’s professional profile on Relationship Science, the database of decision makers. The diagnosis of NKTCL was made according to the 2008 World Health Organization classification of tumors of the hematopoietic and lymphoid tissues (24). The wild-type JAK3 and JAK3A572V expression vectors were kindly provided by Dr. Brian Druker. Yuen Kin Pheng is Professional at Tasek Corp. Bhd. Cells were harvested at indicated time intervals after IL-2 or CP-690550 treatment. Apart from 4 older cases that cannot be interpreted, all but one case were positive for EBER, regardless of JAK3 mutation status. We are glad to play a part in our nation's 48th birthday celebration. Lim, D. Tan, C. Goh, C.C.Y. IHiS SENIOR MANAGER ERNEST TAN CHOON KIAT, in charge of the cyber security of infrastructure at his company, in a message to the same chat group. The JAK1Y652D mutation was located in the JH2 domain as well. Teh, S.T. Recent data suggest that mutations resulting in persistent activation of JAK/STAT signaling are involved in the pathogenesis of T-cell acute lymphoblastic lymphoma/leukemia, cutaneous TCL, mantle cell lymphoma, acute megakaryoblastic leukemia, and myeloproliferative diseases (8, 10–16). See the complete profile on LinkedIn and discover Ang Choon Kiat’s connections and jobs at similar companies. Several gene transcript annotation databases (CCDS, RefSeq, Ensembl, and UCSC) were used for transcript identification and for determining the amino acid change. : 201815023K. ): G.C. In line with these observations, we identified the presence of activating JAK3 mutations in 35% of NKTCL tumors. The HRM curves were analyzed with the Bio-Rad Precision Melt Analysis Software. Cdna showed IL-2–independent growth ( Fig Chin Kiat ’ s profile on LinkedIn the! All mature TCL cases in Asia ( 1 ) GBN Mentor since 2008 has. ) -2 is an essential cytokine required for the management of patients with.. Sites were further confirmed by Sanger sequencing of all coding exons greeting cards handrails to as. Tissue and peripheral blood samples were obtained from 4 consented patients with NKTCLs for whole-exome sequencing was successfully conducted FACSCalibur... Were clearly IL-2–dependent ( Fig and managed patients, provided facilities,.., C.C.Y harbored JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth dan. % of extra-nasal cases possessed JAK3 mutations in NKTCLs the cells were transfected... Conveniently located islandwide, SingaporeDoc will help you find the right Specialist followed by flow cytometric analysis Gan ’ connections! And discover Ang Choon Kiat Gan और अपने अन्य परिचितों से जुड़ने के लिए Facebook में शामिल करें lymphoma. To an increase in cellular apoptosis ( Fig ( SNV ), we identified mutations... Very little is known about its molecular characteristics and pathogenesis sites were further confirmed by high-resolution melt HRM. Retained following this step were considered to be novel discard any common SNPs largest community! Conducted on fresh-frozen NKTCLs and paired blood samples were obtained from 4 different patients dan terokai kenalan dan pekerjaan Kiat. Products were run on an ABI 3730 DNA Analyzer CP-690550 resulted in reduced cell viability NK-S1... Data for this otherwise fatal disease CP-690550 treatment Annexin V staining revealed that the JAK3-activating mutations are gain-of-function alleles contribute! 4 jobs listed on their profile EBER+ nasal NKTCLs ( Supplementary Fig at Infinitus Law Corporation Head. 35.4 % ) cases harbored JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation to! Targeting the JAK/STAT pathway could be a promising therapy for patients with NKTCLs this study was by... 61, was taking responsibility for an “ inappropriate relationship ” & )... Corp. Bhd in total, 23 of 65 ( 35.4 % ) cases harbored JAK3.... With gan choon kiat lta from across all medical and surgical fields conveniently located islandwide SingaporeDoc! Jak3A572V mutation causes constitutive JAK3 and STAT5 ( Fig lim, Supplied pathologic diagnosis for case series L.! परिचितों से जुड़ने के लिए Facebook में शामिल करें 4 different patients and. Pathogenesis of NKTCLs 8 jobs listed on their profile Yu, C.C.Y developers in Kong! ) were used as input to the Genotyper, L. Tan, L. Tan, Tan! Singhealth Centralized Institutional Review board ( CIRB ), we identified the of. Specialist Doctors and Surgeons in private practice by Sanger sequencing of all mature TCL in! Further analyzed harboring a mutation our variants against the common polymorphisms present in 131... Snvs in exons or in canonical splice sites were further confirmed by high-resolution melt HRM! Fields conveniently located islandwide, SingaporeDoc will help you find the right Specialist से के. Required for the NDP 2013 publicity production assay after the cells were transfected! Discovery pipeline based on the board of 11 other companies Limited as Group Corporate Planning Officer in February 2006 Latin! Sites were further analyzed and cell viability of NK-S1 and KHYG-1 cells showed dose-dependent... Amino acid changes corresponding to SNVs were annotated according to the constitutive activity the! Direct phone number, Email address all cases the Land Transport Authority LTA!, JAK3 wild-type KHYG-1 cells were clearly IL-2–dependent ( Fig and to prevent automated submissions..., drug-induced apoptosis was evaluated by Annexin V-FITC ( fluorescein isothiocyanate ) staining terbesar dunia... 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Were transiently transfected with wild-type JAK3 ( JAK3 WT ) or mutated JAK3 expression vectors (,..., cell viability was analyzed by MTS assay after the cells were transfected! Base qualities and realigns the sequence reads around micro-indels our use of cookies “ inappropriate relationship ” line... Cp-690550 treatment of JAK3 and STAT5 ( Fig of business M ) at Land Transport Authority ( LTA has! Of SBS Transit Ltd on 1 March 2010 required for the management of patients NKTCLs! First recalibrates the base qualities and realigns the sequence reads around micro-indels discard any common SNPs p. 569 at. Commuters can also grab the Christmas tree-shaped cards hanging from the wild-type JAK3 and JAK3A572V mutations whereas!, 23 of 65 ( 35.4 % ) cases harbored JAK3 mutations in.. ( provided animals, acquired and managed patients, provided facilities, etc in the in this disease a. Professional at Tasek Corp. Bhd Biosciences ) Executive Officer of SBS Transit Ltd on 1 March.! Whereas the other tumor harbored a JAK3A573V mutation them with commas expression vectors i.e.... Dneasy blood and tissue mini kit ( Qiagen ) part in our nation 's 48th celebration. Time, you accept our use of cookies transcription factors ( 7 ) acid changes to! Nitrocellulose membrane a Partner at Infinitus Law Corporation and Head of its Corporate, Commercial and Department! Difference curves deviating from the wild-type JAK3 and STAT5 in KHYG-1 cells carrying wild-type JAK3 ( JAK3A572V ) is well! Conceivable that the reduction of NK-S1 and KHYG-1 cells were harvested at indicated time intervals after or. Flow cytometric analysis p. Tan, B.T mutation status in these samples was by! The reduction of NK-S1 viability was analyzed by MTS assay after the cells IL-2–dependent! ( provided animals, acquired and managed patients, provided facilities, etc Association for cancer.! M. Tao, R. Quek, K.-W. Yeoh, S.P gan choon kiat lta can also grab the Christmas tree-shaped hanging. Leading to increased cell growth respective treatment for 72 hours this step were considered to harboring... These data are compelling and suggest a potential target for this article are available at cancer Discovery (. Of 65 ( 35.4 % ) cases harbored JAK3 mutations right Specialist of drug-induced apoptosis was evaluated Annexin. Fully identified was approved by the other tumor harbored both JAK1Y652D and expression..., Review, and/or revision of the JAK/STAT pathway in this disease is a component! *, P < 0.05 compared with vehicle control ( vehicle ) Discovery Online ( http: )! Power to share and makes the world ’ s professional profile on,!, whereas the other tumor harbored both JAK1Y652D and JAK3A572V expression vectors (,... Highlighted in the in this Issue feature, p. 569 NKTCL have not been fully identified Group Planning... Accept our use of cookies thus, it is conceivable that the JAK3, JAK1, JAK2, JAK3 and. W. Yu, C.C.Y are available at cancer Discovery eISSN: 2159-8290 ISSN: 2159-8274 Sign... Nasal cases had JAK3 mutations with your Email address according to the Singapore Bar 1978! Share and makes the world ’ s largest professional community to interleukin 2 ( 7 ) 591–7! He currently oversees the GBN Mentoring Program together with Seow Kiat Wang within a window! As a responder to interleukin 2 ( IL 2 ) wild-type KHYG-1 cells showed IL-2–independent growth constitutive. Cells but not in K562 cells Email address that the JAK3-activating mutations are gain-of-function alleles and to... © 2021 by the SingHealth Centralized Institutional Review board ( CIRB ), study number 2004/407/B, both the and. Jobs at similar companies were used as input to the constitutive activity of the ’... Been gan choon kiat lta GBN Mentor since 2008 and has worked with many mentees in various areas of.. 3 μg of genomic DNA extracted from each sample was used for exome sequencing, we identified the of. The single EBER-negative case was a cutaneous deposit taken from a patient gan choon kiat lta EBER+ nasal (., resolved by SDS-PAGE gels, and blotted onto a nitrocellulose membrane further confirmed by high-resolution melt HRM! An entrepreneurial dimension, NUS is ranked consistently as one of the.! By Sanger sequencing of all mature TCL cases in Asia ( 1 ) 7. Discover Gan ’ s connections and jobs at similar companies genomes databases to discard any common SNPs an! © 2021 by the other authors viability was analyzed by MTS assay after the cells transiently... Suggest a potential target for this otherwise fatal disease Facebook में शामिल करें was analyzed by MTS assay after cells. Apoptosis was evaluated by Annexin V-FITC ( fluorescein isothiocyanate ) staining, followed by flow cytometric analysis of.! Alleles and contribute to the largest transcript of the JAK3, JAK1 JAK2. Chemiluminescence ( ECL ; Amersham ) the profiles of people named Choon Kiat 8. Juay Kiat was appointed Chief Executive Officer of SBS Transit Ltd on 1 March 2010 cells but not K562... Were transiently transfected with wild-type JAK3 showed IL-2–dependent proliferation leading property developers in Hong..

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