The Haematological Malignancy Genomics Laboratory operates a comprehensive translational research program in haematological malignancies with focus on multiple myeloma (MM), acute myeloid leukemias (AML) and natural killer / T-cell Lymphoma (NKTL). At the core of this program is the use of high-throughput cutting edge genomics and proteomics techniques in human tumor samples and model system to make clinically relevant discoveries. These discoveries will encompass novel biological insights, identification of new diagnostic subtypes, prognostic factors, therapeutic targets, and aspects of molecular epidemiology and pharmacogenomics, all with potential impact on patient care. In this bench-to-bedside translational pipeline, discoveries are validated in the pre-clinical setting before clinical validation. The program will be supported by a comprehensive tissue bank that provides high-quality source materials for down-stream study, and a clinical database that is connected by a relational database for integrated system biology analysis (See Figure Below). In MM, we are focused on identifying the pathways leading to disease progression. In this regard, we have constructed step-wise pathways of progression for MM and is using this as a framework to design therapeutic intervention strategy. At the same time, we are using genomics to dissect the molecular heterogeneity of the disease. This has yielded robust genetic subtypes. We are now focusing on rationally targeting high-risk subtypes based on the underlying genomic aberrations and molecular defects. In AML, we have been working on mechanisms mediating therapeutic resistance in FLT3 positive AML, and in the process have identified novel molecules that play a fundamental role in leukemogenesis and may represent novel therapeutic targets. In addition, we are also testing novel compounds targeting EZH2, an oncogenic histone modifier, and has unravelled interesting biology in AML so far. In NKTL, we are using genomics to understand key molecular event mediating pathophysiology. Till now, we have identified key pathways that are activated and showed that most of these pathway activations are due to downregulation of regulating miRNAs. The downregulation of these miRNAs are mediated by EBV infection or MYC activation. We have also identified certain markers that are universally over-expressed in NKTL and may serve as novel therapeutic targets.

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2. Chong PSY, Chooi JY, Lim JSL, Toh SHM, Tan TZ, Chng WJ*. SMARCA2 Is a Novel Interactor of NSD2 and Regulates Prometastatic PTP4A3 through Chromatin Remodeling in t(4;14) Multiple Myeloma. Cancer Res. 2021 May 1;81(9):2332-2344.

3. Jia Y, Zhou J, Tan TK, Chung TH, Wong RWJ, Chooi JY, Lim JSL, Sanda T, Ooi M, De Mel S, Soekojo C, Chen Y, Zhang E, Cai Z, Shen P, Ruan J, Chng WJ*. Myeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma. Blood Cancer J. 2021 Feb 12;11(2):32

4. Zhou J, Yiying Quah J, Ng Y, Chooi JY, Hui-Min Toh S, Lin B, Zea Tan T, Hosoi H, Osato M, Seet Q, Ooi LAG, Lindmark B, McHale M, Chng WJ*. ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia. Haematologica. 2020 Sep 1;105(9):2286-2297.

5. Li B, Yan J, Phyu T, Fan S, Chung TH, Mustafa N, Lin B, Wang L, Eichhorn PJA, Goh BC, Ng SB, Kappei D, Chng WJ*. MELK mediates the stability of EZH2 through site-specific phosphorylation in extranodal natural killer/T-cell lymphoma. Blood. 2019 Dec 5;134(23):2046-2058.

6. Teoh PJ, Chung TH, Chng PYZ, Toh SHM, Chng WJ*. IL6R-STAT3-ADAR1 (P150) interplay promotes oncogenicity in multiple myeloma with 1q21 amplification. Haematologica. 2020 May;105(5):1391-1404.

7. Chong PSY, Zhou J, Lim JSL, Hee YT, Chooi JY, Chung TH, Tan ZT, Zeng Q, Waller DD, Sebag M, Chng WJ*. IL6 Promotes a STAT3-PRL3 Feedforward Loop via SHP2 Repression in Multiple Myeloma. Cancer Res. 2019 Sep 15;79(18):4679-4688.

8. Teoh PJ, An O, Chung TH, Chooi JY, Toh SHM, Fan S, Wang W, Koh BTH, Fullwood MJ, Ooi MG, de Mel S, Soekojo CY, Chen L, Ng SB, Yang H, Chng WJ*. Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis. Blood. 2018 Sep 20;132(12):1304-1317.

9. V Selvarajan, J Yan, MF Ham, M Salto-Tellez, Dominic, Y Ito, WJ Chng*, SB Ng*. Characterization of the biological and clinical relevance of RUNX3 in Natural Killer/T-Cell lymphoma. Leukemia 2017; 31: 2219-2227.

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