Publications by authors named "Anna Mies"
Article Synopsis
- - The EUROPE phase 2 trial examined how well biomarkers predict the effectiveness of romiplostim (ROM) treatment for patients with lower-risk myelodysplastic neoplasms (LR-MDS) and low platelet counts, involving 77 patients from the EMSCO network.
- - Out of the participants, 42% showed significant improvements in platelet counts, lasting a median of 340 days, while other types of responses (neutrophil and erythroid) were much less common.
- - The study found that while certain mutations (like SRSF2) and baseline hemoglobin levels were linked to positive responses, ROM treatment did not affect the progression of genetic mutations in patients, confirming its safety and efficacy.
Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to detect shifts of cellular properties of entire populations.
View Article and Find Full Text PDFThe bone marrow microenvironment (BMME) plays a key role in the pathophysiology of myelodysplastic syndromes (MDS), clonal blood disorders affecting the differentiation, and maturation of hematopoietic stem and progenitor cells (HSPCs). In lower-risk MDS patients, ineffective late-stage erythropoiesis can be restored by luspatercept, an activin receptor type IIB ligand trap. Here, we investigated whether luspatercept can modulate the functional properties of mesenchymal stromal cells (MSCs) as key components of the BMME.
View Article and Find Full Text PDFRigosertib is a novel multi-kinase inhibitor, which has clinical activity towards leukemic progenitor cells of patients with high-risk myelodysplastic syndromes (MDS) after failure or progression on hypomethylating agents. Since the bone marrow microenvironment plays an important role in MDS pathogenesis, we investigated the impact of rigosertib on cellular compartments within the osteo-hematopoietic niche. Healthy C57BL/6J mice treated with rigosertib for 3 weeks showed a mild suppression of hematopoiesis (hemoglobin and red blood cells, both - 16%, p < 0.
View Article and Find Full Text PDFBackground: Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) are hematological stem cell diseases mainly of the elderly. Studies indicate a close relationship between bone metabolism and hematopoietic stem cells within the osteo-hematopoietic niche. However, it remains unclear how the disturbed interaction within the osteo-hematopoietic niche affects bone homeostasis in MDS and AML patients.
View Article and Find Full Text PDFArticle Synopsis
- * Treatment focuses on improving anemia and managing iron overload from frequent red blood cell transfusions, often utilizing erythropoiesis-stimulating agents (ESAs) like erythropoietin (EPO).
- * While ESAs are effective in about half of patients, their effects may be short-lived; newer drugs like sotatercept and luspatercept offer hope by promoting better red blood cell production and differentiation.
Activin Receptor II Ligand Traps and Their Therapeutic Potential in Myelodysplastic Syndromes with Ring Sideroblasts.
Curr Hematol Malig Rep
December 2016
Article Synopsis
- Distinct subtypes of lower risk myelodysplastic syndromes are characterized by ring sideroblasts, which are erythroid progenitors with excess iron in their mitochondria, often linked to mutations in splicing machinery.
- Standard treatments, like erythropoiesis-stimulating agents, often don't effectively improve erythroid function in these patients due to issues in late-stage red blood cell development.
- The review proposes new therapies using activin receptor ligand traps that target abnormal TGF-β signaling to enhance red blood cell differentiation and alleviate anemia in sideroblastic subtypes of myelodysplastic syndromes.
Hematopoietic and mesenchymal stem and progenitor cells are organized in the osteo-hematopoietic niche, a complex microenvironment ensuring self-renewal and differentiation. Perturbations of the niche architecture, the mutual cellular interactions and signaling pathways disrupt tissue homeostasis resulting in cytopenia and malignant diseases such as myelodysplastic syndromes (MDS), supporting the concept of niche-induced oncogenesis. Analyzing the available treatment options for patients harboring MDS, it becomes evident that many of them specifically modify components of the stem cell niche.
View Article and Find Full Text PDFA significant portion of newly synthesized protein fails to fold properly and is quickly degraded. These defective ribosomal products (DRiPs) are substrates for the ubiquitin-proteasome system (UPS) and give rise to a large fraction of peptides presented by major histocompatibility complex class I molecules (MHCI). Here, we showed that DRiPs are also autophagy substrates, which accumulate upon autophagy inhibition in aggresome-like-induced structures (ALIS).
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