Publications by authors named "Daryl Cheah"

Article Synopsis
  • - Natural killer/T-cell lymphoma (NKTL) is a rare and aggressive form of non-Hodgkin's lymphoma that has poor treatment options, leading to a need for new therapies like the HDAC inhibitor chidamide, which is currently approved for other types of T-cell lymphoma.
  • - A phase II clinical trial involving 28 NKTL patients showed that chidamide has promising efficacy, with a 39% overall response and an 18% complete response rate, but resistance was linked to overactive JAK-STAT signaling in cancer cells.
  • - Combining chidamide with a JAK inhibitor (ruxolitinib) can help overcome resistance, and the study identified CD30 (TNFRSF8) as a
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Mucosa-associated lymphoid tissue (MALT) lymphoma is a B-cell tumour that develops over many decades in the stomachs of individuals with chronic Helicobacter pylori infection. We developed a new mouse model of human gastric MALT lymphoma in which mice with a myeloid-specific deletion of the innate immune molecule, Nlrc5, develop precursor B-cell lesions to MALT lymphoma at only 3 months post-Helicobacter infection versus 9-24 months in existing models. The gastric B-cell lesions in the Nlrc5 knockout mice had the histopathological features of the human disease, notably lymphoepithelial-like lesions, centrocyte-like cells, and were infiltrated by dendritic cells (DCs), macrophages, and T-cells (CD4 , CD8 and Foxp3 ).

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Article Synopsis
  • Combination therapy is currently the standard treatment for relapsed/refractory non-Hodgkin's lymphoma (RR-NHL), but response rates are often low, especially in patients resistant to chemotherapy.
  • Researchers evaluated a new method called quadratic phenotypic optimization platform (QPOP), which can predict effective drug combinations using limited tumor samples from RR-NHL patients.
  • In a study involving 71 patients, QPOP-guided treatments showed improved outcomes and fewer cases of disease progression compared to traditional chemotherapy, providing a strong basis for future clinical trials on this approach.
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With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients. Here, we used next-generation sequencing to sequence 260 NKTCL tumors, and trained a genomic prognostic model (GPM) with the genomic mutations and survival data from this retrospective cohort of patients using LASSO Cox regression. The GPM is defined by the mutational status of 13 prognostic genes and is weakly correlated with the risk-features in International Prognostic Index (IPI), Prognostic Index for Natural-Killer cell lymphoma (PINK), and PINK-Epstein-Barr virus (PINK-E).

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Diffuse large B-cell lymphoma (DLBCL) exhibits frequent inactivating mutations of the histone acetyltransferase CREBBP, highlighting the attractiveness of targeting CREBBP deficiency as a therapeutic strategy. In this study, we demonstrate that chidamide, a novel histone deacetylase (HDAC) inhibitor, is effective in treating a subgroup of relapsed/refractory DLBCL patients, achieving an overall response rate (ORR) of 25.0% and a complete response (CR) rate of 15.

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Whole genomic and transcriptomic analyses of MEITL revealed multiple potential therapeutic targets. Synergistic effects of pimozide and romidepsin are shown in a well-characterized MEITL PDX model.

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Article Synopsis
  • Extranodal natural killer T-cell lymphoma (NKTCL) is a highly aggressive cancer, especially common in Asian and Latin American populations, with Epstein-Barr virus and HLA-DPB1 gene variants being linked to its risk.
  • A genome-wide association study was conducted involving 700 NKTCL cases and over 7,700 controls from various regions in China, along with additional samples from Hong Kong and other Asian countries, to identify genetic variants that contribute to NKTCL susceptibility.
  • The study discovered two significant genetic loci associated with NKTCL: IL18RAP on chromosome 2 and HLA-DRB1 on chromosome 6, indicating that these genetic factors may increase the risk of developing this lymphoma
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Extranodal NK/T-cell lymphoma, nasal type (NKTL) is an aggressive type of non-Hodgkin lymphoma closely associated with Epstein-Barr virus and characterized by varying degrees of systemic inflammation. We aim to examine the prognostic significance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTL. Therefore, we conducted a retrospective review of 178 patients with biopsy-proven NKTL from the National Cancer Centre Singapore and Samsung Medical Center, South Korea.

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Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae.

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Mature T-cell lymphomas, including peripheral T-cell lymphoma (PTCL) and extranodal NK/T-cell lymphoma (NKTL), represent a heterogeneous group of non-Hodgkin lymphomas with dismal outcomes and limited treatment options. To determine the extent of involvement of the JAK/STAT pathway in this malignancy, we performed targeted capture sequencing of 188 genes in this pathway in 171 PTCL and NKTL cases. A total of 272 nonsynonymous somatic mutations in 101 genes were identified in 73% of the samples, including 258 single-nucleotide variants and 14 insertions or deletions.

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