Yiting Yu

Yiting Yu
Middlesex University, UK · Art and Design Research Institute (ADRI)

About

88
Publications
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Publications

Publications (88)
Article
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Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with ov...
Article
Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexp...
Article
Epigenetic changes in cancer are thought to contribute to the regulation of invasion and metastasis. To study this at a genome-wide level in melanoma, we analyzed the methylome of 44 cases of malignant melanoma. We saw widespread demethylation occurring preferentially outside of CpG islands. Comparison of primary and metastatic lesions showed demet...
Article
Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell l...
Article
Full-text available
Objectives Follicular lymphoma (FL) is the most common indolent B cell lymphoma in the United States and a quarter of patients present with stage I disease. The objective of this study was to examine if primary site of disease influences survival in early stage lymphoma. Results The most common extranodal primary sites were the integumentary syste...
Article
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The bone marrow microenvironment influences malignant hematopoiesis but how it promotes leukemogenesis has not been elucidated. Additionally, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-d...
Article
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. We conducted a transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls and observed an overexpression of NOTCH ligands [JAGGED1, JAGGED2) and Delta like (DLL3) family of ligands] and receptors (NOTCH...
Article
Epigenetic changes in cancer are thought to contribute to regulation of invasion and metastasis. To study this at a genome-wide level in melanoma we analyzed the methylome of 44 cases of malignant melanoma. We saw widespread demethylation in melanoma occurring preferentially outside of CpG islands. Comparison of primary and metastatic lesions showe...
Article
Full-text available
Exposure to a high fat (HF) diet in utero is associated with increased incidence of cardiovascular disease (CVD), diabetes and metabolic syndrome later in life. However, the molecular basis of this enhanced susceptibility for metabolic disease is poorly understood. Gene expression microarray and genome-wide DNA methylation analyses of mouse liver r...
Article
Full-text available
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activ...
Article
Full-text available
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) suppress normal hematopoietic activity in part by enabling a pathogenic inflammatory milieu in the bone marrow. In this report, we show that elevation of angiopoietin-1 in myelodysplastic CD34+ stem-like cells is associated with higher risk disease and reduced overall survival in MDS...
Article
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Although absolute neutrophil counts (ANC) below 1.5×10³/uL are used to define neutropenia as a marker of increased susceptibility to infections, their relationship with survival has not been examined. Since low counts trigger extensive investigations, determining prognostic cutoffs especially for different ethnicities and races is critical. A multi...
Article
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Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesi...
Article
Genomic studies have shown that human cancer is rarely associated with a complete loss of transcripts; instead, acquired DNA alterations often occur within the non-coding part of the genome, are enriched in gene-regulatory regions, and cause only moderate transcriptional changes. It is currently not well understood how such moderate gene expression...
Article
Background Life expectancy of patients with Polycythemia Vera is reduced compared with the general population. History of thrombosis has been found to be the main predictor of death in this disease. Factors like older age, leukocytosis and thrombosis have been shown to increase the risk of mortality. Secondary polycythemia on the other hand is larg...
Article
Full-text available
Recurrent somatic mutations of the epigenetic modifier and tumor suppressor ASXL1 are common in myeloid malignancies, including chronic myeloid leukemia (CML), and are associated with poor clinical outcome. CRISPR/Cas9 has recently emerged as a powerful and versatile genome editing tool for genome engineering in various species. We have used the CR...
Article
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Anemia is the predominant clinical manifestation of myelodysplastic syndromes (MDS). Loss or deletion of chromosome 7 is commonly seen in MDS and leads to a poor prognosis. However, the identity of functionally relevant, dysplasia-causing, genes on 7q remains unclear. Dedicator of cytokinesis 4 (DOCK4) is a GTPase exchange factor, and its gene maps...
Article
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We identified amplification of RICTOR, a key component of the mTORC2, as the sole actionable genomic alteration in an 18-year-old never smoker with lung adenocarcinoma. It occurs in 13% of lung cancers (1016 cases) in TCGA and at a similar frequency in an independent cohort of 1,070 patients identified by genomic profiling. In the latter series, 11...
Article
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Modest transcriptional changes caused by genetic or epigenetic mechanisms are frequent in human cancer. Although loss or near-complete loss of the hematopoietic transcription factor PU.1 induces acute myeloid leukemia (AML) in mice, a similar degree of PU.1 impairment is exceedingly rare in human AML; yet, moderate PU.1 inhibition is common in AML...
Article
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Poor clinical outcome of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) has been attributed to failure of current chemotherapeutic regimens to target leukemic stem cells. We recently identified p21-activated kinase (PAK1) as a downstream effector molecule of H2.0-like homeobox (HLX), a gene functionally relevant for AML pathogenesi...
Article
Full-text available
The methylcytosine dioxygenase TET1 ('ten-eleven translocation 1') is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted t...
Article
AML and MDS are associated with disease initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against pre-leukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML and co...
Article
The marrow microenvironment contributes to the pathogenesis of ineffective hematopoiesis in Myelodysplastic Syndromes (MDS). Since mutations and cytogenetic alterations seen in the hematopoietic compartment are generally not present in marrow stromal cells, we hypothesized that epigenetic alterations may be responsible for altered stroma function i...
Article
Background: Follicular lymphoma (FL) is the most common indolent B cell lymphoma with a rising incidence. Approximately 26% of patients with FL present with stage I disease. Although international consensus guidelines recommend radiotherapy for these patients, a recent survey of the National Lymphocare Study demonstrated that adherence to the stand...
Article
Background: A neutrophil count of 1500 cells per microliter has been traditionally used as the cutoff for neutropenia and has been considered a marker of increased susceptibility to infections and adverse prognosis. Despite conventional use of this definition, there are no large studies that have examined the direct relationship of low neutrophil c...
Article
The POT1 gene is located in chromosome 7 and encodes a key component of the shelterin complex, which is essential for the maintenance of telomere and chromosome integrity. Somatic mutations of POT1 have been identified in chronic lymphocytic leukemia, which indicates that POT1 dysfunction is involved in the pathogenesis of hematological neoplasms....
Article
Introduction: Recent approval of second generation tyrosine kinase inhibitors (TKI) in chronic myelogenous leukemia (CML) has raised issues about their efficacy and pharmaco-economic utility in front line therapy of CML. We aimed to study these issues as well as reasons for switching TKIs in a real world setting of inner-city, multi-ethnic, underse...
Article
Introduction- MDS and AML are hematologic malignancies that are characterized by malignant cell expansion and suppression of normal hematopoietic activity. An inflammatory cytokine milieu in the marrow has been implicated in suppression of normal hematopoietic activity in MDS and AML. Since cytopenias are a major source of morbidity, these incurabl...
Article
Current chemotherapeutic approaches in AML and MDS target rapidly dividing cells, having limited effects on the leukemic and preleukemic stem cells responsible for disease propagation and relapse. Novel therapies that are able to target (pre)leukemic stem cells are urgently needed to maintain remission and improve survival in AML and MDS. We recent...
Article
Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS) arise from accumulation of multiple stepwise genetic and epigenetic changes in hematopoietic stem cells (HSC) and/or committed progenitors. A series of transforming events can initially give rise to pre-leukemia stem cells (pre-LSC) as well as fully transformed leukemia stem cells (LSC...
Article
Introduction Familial MDS is a rare disease and has been associated with mutations in multiple genes including GATA2. Mixed Lineage Leukemia 3 (MLL3) encodes a histone methylase that is a tumor suppressor and implicated in poor prognosis in MDS and AML. It occurs at high frequency and across multiple tissue types in genomic surveys of somatic mutat...
Article
Myelodysplastic syndromes (MDS) are hematologic malignancies characterized by hematopoietic stem cell dysfunction that leads to ineffective hematopoiesis and cytopenias. Even though a third of MDS cases transform to leukemia, most of the mortality in MDS is due to low blood counts that occur because of failure of hematopoiesis. Development of effec...
Article
Epigenetic alterations can direct carcinogenesis by leading to transcriptional changes and inducing genomic instability. We analyzed the methylome of malignant melanoma and observed widespread loss of DNA methylation that was found to preferentially occur outside of CpG islands. Demethylation was seen to occur early during carcinogenesis, was indep...
Article
Full-text available
Little is known about the epidemiology of MDS in minority populations. The IPSS and newly released IPSS-R are important clinical tools in prognostication of patients with MDS. Therefore, we conducted a retrospective epidemiological analysis of MDS in an ethnically diverse cohort of patients. Demographics, disease characteristics, and survival were...
Article
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Purpose: Even though recent studies have shown that genetic changes at enhancers can influence carcinogenesis, most methylomic studies have focused on changes at promoters. We used renal cell carcinoma (RCC), an incurable malignancy associated with mutations in epigenetic regulators, as a model to study genome-wide patterns of DNA methylation at a...
Article
Full-text available
The ten-eleven-translocation 5-methylcytosine dioxygenase (TET) family of enzymes catalyzes the conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), a modified cytosine base that facilitates gene expression. Cells respond to hypoxia by inducing a transcriptional program regulated in part by oxygen-dependent dioxygenases that re...
Article
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Even though alterations in platelet counts are presumed to be detrimental, their impact on patient survival has not been studied in large cohorts. The prevalence of thrombocytopenia and thrombocytosis were examined in a large inner city outpatient population of 36262 individuals aged ≥65 years old. A significant association with shorter overall sur...
Article
Full-text available
Acute myeloid leukemia (AML) is characterized by disruption of HSC and progenitor cell differentiation. Frequently, AML is associated with mutations in genes encoding epigenetic modifiers. We hypothesized that analysis of alterations in DNA methylation patterns during healthy HSC commitment and differentiation would yield epigenetic signatures that...
Article
Full-text available
Hematopoietic stem cell differentiation involves the silencing of self-renewal genes and induction of a specific transcriptional program. Identification of multiple covalent cytosine modifications raises the question of how these derivatized bases influence stem cell commitment. Using a replicative primary human hematopoietic stem/progenitor cell d...
Article
Barrett's epithelium (BE) is a premalignant condition resulting from chronic gastroesophageal reflux that may progress to esophageal adenocarcinoma (EAC). Early intervention holds promise in preventing BE progression. However, identification of high-risk BE patients remains challenging due to inadequate biomarkers for early diagnosis. We investigat...
Article
Introduction Anisocytosis is defined as excessive variation in the size of red cells. It can be quantified by measuring the red cell distribution width (RDW) and is routinely included in peripheral blood count reports. Anisocytosis has previously been associated with poorer prognosis in patients with coronary artery disease, congestive heart failur...
Article
Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS) arise from accumulation of multiple stepwise genetic and epigenetic changes in hematopoietic stem cells (HSC) and/or committed progenitors. A series of transforming events can initially give rise to pre-leukemia stem cells (pre-LSC) as well as fully transformed leukemia stem cells (LSC...
Article
Recent studies have shown that an elevated red cell distribution width (RDW) is an important predictor of adverse outcomes. However, the strength of this biomarker has not been tested in a large outpatient elderly population. Also since increased RDW can be due to a variety of etiologies, additional biomarkers are needed to refine the prognostic va...
Conference Paper
Introduction Anisocytosis is defined as excessive variation in the size of red cells. It can be quantified by measuring the red cell distribution width (RDW) and is routinely included in peripheral blood count reports. Anisocytosis has previously been associated with poorer prognosis in patients with coronary artery disease, congestive heart failur...
Article
Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of oesophageal adenocarcinoma (EAC) and its progression. lncRNAs that are abnormally upregulated in EACs were identified by...
Article
The bone marrow microenvironment plays an important role in the pathogenesis and perpetuation of stem cell defects in Myelodysplastic Syndrome (MDS). However, while distinct cytogenetic alterations have been described in the stem cell compartment in MDS, the bone marrow (BM) stroma has never been shown to be part of the clone. Thus, aberrant epigen...
Article
Diffuse large B cell lymphoma (DLBCL) is the most common type of B cell malignancy in the adult population. Based on their patterns of gene expression, DLBCLs can be divided into two major subgroups: the germinal center (GC) B cell like (GCB-DLBCL) and the activated B cell like (ABC-DLBCL) cases. Current studies suggest that the cell-of-origin for...
Article
Full-text available
5-hydroxymethylcytosine (5-hmC) is a recently discovered epigenetic modification that is altered in cancers. Genome-wide assays for 5-hmC determination are needed as many of the techniques for 5-methylcytosine (5-mC) determination, including methyl-sensitive restriction digestion and bisulfite sequencing cannot distinguish between 5-mC and 5-hmC. G...
Article
7125 Background: The International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) are used to assess prognosis after diagnosis of myelodysplastic syndromes (MDS). They are based on cytogenetics, bone marrow (BM) blasts, and number and degree of cytopenias. This retrospective analysis examined racial disparities in the presentation a...
Conference Paper
The microenvironment where a tumor originates plays an important role in its initiation, growth, progression and metastatic capability. Since in most cancers the microenvironment is not derived from the malignant clone and does not contain oncogenic mutations, it is likely that the tumor microenvironment is reprogrammed epigenetically to support th...
Article
Full-text available
Epigenetic changes play important roles in carcinogenesis and influence initial steps in neoplastic transformation by altering genome stability and regulating gene expression. To characterize epigenomic changes during the transformation of normal plasma cells to myeloma, we modified the HpaII tiny fragment enrichment by ligation-mediated PCR assay...
Article
Full-text available
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis that leads to peripheral cytopenias. We observed that SMAD7, a negative regulator of transforming growth factor-beta (TGF-β) receptor-I kinase, is markedly reduced in MDS and leads to ineffective hematopoiesis by overactivation of TGF-β signaling. To determine the cause...
Article
Background & aims: Alterations in methylation of protein-coding genes are associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Dysregulation of noncoding RNAs occurs during carcinogenesis but has never been studied in BE or EAC. We applied high-resolution methylome analysis to identify changes at genomic regions that encod...
Article
Full-text available
Differentiation of hematopoietic stem cells to red cells requires coordinated expression of numerous erythroid genes. To understand the regulatory mechanisms governing lineage commitment we conducted a high resolution methylomic and transcriptomic analysis of six major stages of human erythroid differentiation. We observed widespread epigenetic dif...
Poster
The International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) are used to assess prognosis after diagnosis of myelodysplastic syndromes (MDS). They are based on cytogenetics, bone marrow (BM) blasts, and number and degree of cytopenias. This retrospective analysis examined racial disparities in the presentation and survival of MD...
Article
924 Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders that are commonly characterized by anemia due to ineffective hematopoiesis. Even though a third of patients with MDS may transform to acute leukemias, cytopenias drive morbidity for most patients. Anemia remains a major cause of morbidity from fatigue. Most of the mor...
Article
Full-text available
5150 Recent studies have shown that an elevated red cell distribution width (RDW) is an important predictor of adverse outcomes in a variety of clinical settings. The etiologies of an elevated RDW are different depending on mean corpuscular volume (MCV). If the effect of RDW on mortality differs by MCV (i. e., presence of interaction between RDW an...
Article
4645 Introduction Platelets play a critical role in hemostasis and are also important in the development of pathologic processes including atherosclerosis and arterial thrombosis. Both thrombocytopenia and thrombophilia are common findings in several illnesses including liver diseases, infections, autoimmune disorders and malignancies. However, to...
Article
Full-text available
Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis compared to essential thrombocytosis (ET) or polycythemia vera (PV), the molecular distinctions between these...