Matthias Bartenstein

Matthias Bartenstein
Albert Einstein College of Medicine | AECOM · Department of Developmental and Molecular Biology

Dr. med. univ.

About

50
Publications
4,020
Reads
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958
Citations
Additional affiliations
July 2013 - present
Albert Einstein College of Medicine
Position
  • Graduate Studies
July 2009 - July 2012
Fred Hutchinson Cancer Research Center
Education
August 2012 - August 2017
Albert Einstein College of Medicine
Field of study
  • Biomedical Sciences
September 2002 - June 2009
Medical University of Vienna
Field of study
  • Medicine

Publications

Publications (50)
Article
Full-text available
The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequ...
Article
Introduction The World Trade Center (WTC) disaster exposed first responders to high levels of aerosolized carcinogens (Lioy et. al. Env. Health Perspect 2002). Clonal hematopoiesis is associated with exposure to smoking and genotoxic stimuli (Jaiswal et. al. NEJM 2014; Genovese et. al. NEJM 2015). We sought to determine its incidence in WTC-exposed...
Article
Full-text available
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
The MLL3 gene has been shown to be recurrently mutated in many malignancies including in families with acute myeloid leukemia. We demonstrate that many MLL3 variant calls made by exome sequencing are false positives due to misalignment to homologous regions, including a region on chr21, and can only be validated by long-range PCR. Numerous other re...
Article
Full-text available
Acute Myeloid Leukemia and Myelodysplastic Syndromes are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Transcriptomic analysis of stem and progenitor populations in MDS and AML demonstrated overexpression of STAT3 that was validated in an independent cohort. STAT3 overexpression was predictive of a...
Article
Adult T-cell leukemia lymphoma (ATLL) is a rare T cell neoplasm that is endemic in Japanese, Caribbean, and Latin American populations. Most North American ATLL patients are of Caribbean descent and are characterized by high rates of chemo-refractory disease and worse prognosis compared with Japanese ATLL. To determine genomic differences between t...
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
Full-text available
Background: Sweet's syndrome (SS) is a febrile neutrophilic dermatosis that has been clinically linked to hematological malignancies, particularly myelodysplastic syndrome (MDS), in a number of case series. Many epigenetic changes underlying MDS have been identified, such as a mutation in the isocitrate dehydrogenase 1 (IDH1) gene, which causes DN...
Article
Full-text available
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
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
Myelofibrosis (MF) is a common feature of the Philadelphia-Chromosome negative (Ph-) myeloproliferative neoplasms (MPN), a group that includes Primary Myelofibrosis (PMF), Essential Thrombocytosis (ET) and Polycythemia Vera (PV). Current treatment with Jak2 inhibitors reduces splenomegaly, but does not eliminate malignant clones nor improve bone ma...
Article
Full-text available
Mutations of the splicing factor-encoding gene U2AF1 are frequent in the myelodysplastic syndromes (MDS), a myeloid malignancy, and other cancers. Patients with MDS suffer from peripheral blood cytopenias, including anemia, and an increasing percentage of bone marrow myeloblasts. We studied the impact of the common U2AF1$^{S34F}$ mutation on cellul...
Article
Mutations of the splicing factor-encoding gene U2AF1 are frequent in the myelodysplastic syndromes (MDS), a myeloid malignancy, and other cancers. Patients with MDS suffer from peripheral blood cytopenias, including anemia, and an increasing percentage of bone marrow myeloblasts. We studied the impact of the common U2AF1S34F mutation on cellular fu...
Article
Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in...
Article
Myelodysplastic syndrome (MDS) & Acute Myeloid Leukemia (AML) arise from a population of aberrant hematopoietic stem cells (HSCs) that have been altered by multiple genetic & epigenetic alterations. A preliminary genomewide transcriptomic and epigenomic analysis of stem and progenitor cells from MDS and AML patients revealed STAT3 upregulation with...
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
Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights int...
Article
B ackground: Bone marrow fibrosis is associated with poor prognosis in myeloproliferative neoplasms (MPN). Both polycythemia vera (PV) and essential thrombocythemia (ET) patients are at high risk for transformation into myelofibrosis. Although JAK2 inhibitors are effective treatment for MPNs, they are unable to alleviate the fibrotic phenotype. Sin...
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
Full-text available
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
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
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
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
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...
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
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
Hematopoietic cell transplantation (HCT) offers potentially curative therapy for patients with myelodysplastic syndrome (MDS). However, as the majority of patients with MDS is in the 7th or 8th decade of life, only few of these patients were transplanted following high-dose conditioning regimens. The development of reduced-intensity conditioning ha...
Article
Full-text available
Interleukin (IL)-32 was originally identified in natural killer cells and IL-2-activated human T lymphocytes. As T cells are activated in allogeneic transplantation, we determined the role of IL-32 in human mixed lymphocyte cultures (MLCs) and GVHD. In allogeneic MLCs, IL-32 increased two-fold in responding T cells, accompanied by five-fold increas...
Article
Full-text available
Currently, the conceptualization and treatment of personality pathologies are mainly theory driven. The resulting categorical classification of personality disorders leads to inaccurate diagnoses and is therefore being criticized by many researchers and clinicians. A consensus exists that in the upcoming edition of the DSM (DSM 5), the classificati...
Article
Hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for patients with myelodysplastic syndromes (MDS). However, as the majority of patients with MDS are in the seventh or eighth decade of life, conventional transplant regimens have been used only infrequently, and only with the development of reduced-intensity conditi...
Chapter
Background: Treatment response and therapy engagement is linked to the process of psychotherapy planning, but treatment response is difficult to be assessed with common, currently used diagnostic instruments. The aim is to investigate factors (patient's affect experience and interpersonal functioning) in the initial psychotherapeutic interview, whi...

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