| Title: |
PS1327 PRO‐NECROPTOTIC RIPK3 AS A STAGE‐DEPENDENT MARKER IN THE BONE MARROW OF PATIENTS WITH MDS AND CMML |
| Authors: |
Dill, V.; Jilg, S.; Wagner, C.; Hauch, R.; Buschhorn, L.; Odinius, T.; Kauschinger, J.; Wahida, A.; Höckendorf, U.; Slotta‐Huspenina, J.; Prodinger, P.; Schmidt, B.; Müller‐Thomas, C.; Haferlach, T.; Kern, W.; Götze, K.; Peschel, C.; Bassermann, F.; Jost, P. |
| Source: |
HemaSphere ; volume 3, issue S1, page 605-606 ; ISSN 2572-9241 2572-9241 |
| Publisher Information: |
Wiley |
| Publication Year: |
2019 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background: Chronic inflammation plays a central role in the development of hematological neoplasms. In Myelodysplastic syndromes (MDS) pro‐inflammatory microenvironment is suspected to drive disease development. Several studies have shown increased rates of programmed cell death in marrow cells of patients with early stage MDS. In these patients improvement of cytopenia is a major therapeutic approach. Overcoming resistance to programmed cell death is a central therapeutic aim in patients with high‐risk MDS/sAML. RIPK3 is a crucial player of regulated necrosis (necroptosis). Necroptosis has a strong inflammatory capacity and pro‐inflammatory processes trigger necroptosis. Aims: The aim of this project is to identify pro‐necroptotic proteins in the bone marrow of patients with MDS, CMML and sAML and to correlate the necroptotic capacity with the stage of the disease. By pharmacological modulation of necroptosis we would like to evaluate the effects of necroptotic signaling on inflammation, cell death and cell differentiation. Methods: We therefore analyzed the impact of pro‐necroptotic signaling on bone marrow bulk and the subset of CD34 + stem/progenitor cells of patients with MDS and chronic myelomonocytic leukemia (CMML ) in vitro . Bone marrow mononuclear cells (BMMNCs) were isolated from BM aspirates of 5 patients with early MDS (MDS‐MLD, MDS‐RS‐SLD and MDS‐RS‐MLD), 5 patients with late MDS (MDS‐EB1 and MDS‐EB2), 5 patients with CMML‐1, 7 patients with CMML‐2 and 4 patients with sAML after a history of MDS and 4 patients with sAML after a history of CMML. Bulk of BMMNCs and purified CD34 + stem/progenitor cells were stained intracellular for RIPK3 and analyzed by flow cytometry. The patient samples were compared to 12 age‐matched BM samples obtained from hip replacement surgery from otherwise healthy individuals. Furthermore, immunohistochemistry was performed in an enlarged cohort of patients. Therefore paraffin embedded bone marrow biopsies of individuals with MDS or CMML‐1/2 were analyzed over time and ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1097/01.hs9.0000563588.10221.90 |
| DOI: |
10.1097/01.HS9.0000563588.10221.90 |
| Availability: |
http://dx.doi.org/10.1097/01.hs9.0000563588.10221.90; https://onlinelibrary.wiley.com/doi/pdf/10.1097/01.HS9.0000563588.10221.90 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.7C95B93B |
| Database: |
BASE |