A5005531458- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Retinoids in leukemia and cellular processes
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Estrogen and related hormone effects
- RNA Interference and Gene Delivery
- Cell death mechanisms and regulation
- Nuclear Structure and Function
- Ferrocene Chemistry and Applications
- Click Chemistry and Applications
- Cancer-related gene regulation
- Fungal Plant Pathogen Control
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- CAR-T cell therapy research
- RNA Research and Splicing
- Renal and related cancers
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Hippo pathway signaling and YAP/TAZ
- Quinazolinone synthesis and applications
- Hematopoietic Stem Cell Transplantation
Cardiff University
2016-2023
Goethe University Frankfurt
2008-2019
Cancer Genetics (United States)
2018
University Hospital Frankfurt
2004-2015
Palmetto Hematology Oncology
2012
Goethe Institute
2012
Munich Leukemia Laboratory (Germany)
2007
DRK-Blutspendedienst Baden-Württemberg - Hessen
2007
Hesse (Germany)
2005
University of Münster
2003
AbstractThe acute myeloid leukemia (AML)-associated translocation products AML1-ETO, PML-retinoic acid receptor alpha (RARα), and PLZF-RARα encode aberrant transcription factors. Several lines of evidence suggest similar pathogenetic mechanisms for these fusion proteins. We used high-density oligonucleotide arrays to identify shared target genes in inducibly transfected U937 cells expressing PML-RARα, or PLZF-RARα. All three proteins significantly repressed the expression 38 induced 14...
Abstract Histone deacetylase inhibitors have attracted considerable attention because of their ability to overcome the differentiation block in leukemic blasts, an effect achieved either alone or combination with differentiating agents, such as all-trans retinoic acid. We previously reported favorable effects potent histone inhibitor valproic acid patients advanced acute myeloid leukemia leading blast cell reduction and improvement hemoglobin. These were accompanied by hypergranulocytosis...
Abstract BACKGROUND Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, induced in vitro differentiation of primary acute myeloid leukemia (AML) blasts, an effect enhanced by all‐trans retinoic (ATRA). Clinical responses to VPA were recently observed patients with myelodysplastic syndrome (MDS). Herein, the authors have described results clinical trial plus ATRA 26 poor‐risk AML. METHODS (5–10 mg/kg starting dose) and (45 mg/m 2 ) administered orally. Low‐dose AraC or hydroxyurea...
Fusion proteins involving the retinoic acid receptor alpha (RAR alpha) and PML or PLZF nuclear protein are genetic markers of acute promyelocytic leukemias (APLs). APLs with PML-RAR PLZF-RAR fusion phenotypically indistinguishable except that they differ in their sensitivity to (RA)-induced differentiation: blasts sensitive RA patients enter disease remission after treatment, while do not. We here report (i) like expression, expression blocks terminal differentiation hematopoietic precursor...
Fusion proteins involving the retinoic acid receptor α (RARα) and PML or PLZF nuclear protein are genetic markers of acute promyelocytic leukemia (APL). APLs with PML-RARα PLZF-RARα fusion differ only in their response to (RA) treatment: t(15;17) (PML-RARα-positive) APL blasts sensitive RA vitro, patients enter disease remission after treatment, while those t(11;17) (PLZF-RARα-positive) do not. Recently it has been shown that complete can be achieved upon treatment arsenic trioxide (As2O3)...
Stem cells play an important role in the pathogenesis and maintenance of most malignant tumors. Acute myeloid leukemia (AML) is a stem cell disease. The inefficient targeting leukemic (LSC) considered responsible for relapse after induction complete hematologic remission (CR) AML. promyelocytic (APL) subtype AML characterized by t(15;17) translocation expression PML/RARalpha fusion protein. Treatment APL with all-trans retinoic acid (ATRA) induces CR, but not molecular (CMR), because...
PurposeAberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes the pathogenesis development ABL-TK inhibitors (TKI). The pathway thus is an attractive therapeutic target but its role negative ALL conjectural. Moreover, functional contribution individual components not established....
Leukotrienes constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body evidence supports an acute role for 5-LO products already during earliest stages pancreatic, prostate, and colorectal carcinogenesis. Several pieces experimental data form basis this hypothesis suggest correlation between expression tumor cell viability. First, several independent studies documented overexpression in primary cells as well established cancer lines. Second,...
Nonsteroidal anti-inflammatory drugs such as sulindac inhibit Wnt signaling, which is critical to maintain cancer stem cell-like cells (CSC), but they also suppress the activity of 5-lipoxygenase (5-LO) at clinically feasible concentrations. Recently, 5-LO was shown be CSC in a model chronic myeloid leukemia. For these reasons, we hypothesized that may offer therapeutic target improve management acute leukemia (AML), an aggressive disease driven by CSCs. Pharmacologic and genetic approaches...
Histone deacetylase inhibitor valproic acid (VPA) was recently shown to enhance proliferation and self-renewal of normal hematopoietic stem cells, raising the possibility that VPA may also support growth leukemic progenitor cells (LPC). Here, maintains a significantly higher proportion CD34+ LPC colony forming units compared control cultures in six AML samples, but selectively reduces cell numbers another sample with expression AML1/ETO. Our data suggest differential effect on small...
Platinum-based drugs are used as cancer chemotherapeutics for the last 40 years. However, drug resistance and nephrotoxicity major limitations of use platinum-based compounds in therapy. Platinum (IV) complexes believed to act platinum prodrugs able overcome some (II) limitations.A number previously sensitized were evaluated their anti-cancer activity by monitoring ability affect proliferation, clonigenicity apoptosis induction Cisplatin sensitive resistant cells. In addition, uptake...