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| Name | Class |
|---|---|
| University Hospital, Bonn | OTHER |
| Universitätsklinikum Leipzig | OTHER |
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The objective of this study is the description of the possible association between genetic mutation/aberration profiles, inflammatory tonus and clinical phenotype based on PROMs and HRQoL. Apart from gaining a better understanding of the causal correlation between genetics, sterile inflammatory processes and QoL (e.g. fatigue) in MDS, this study is supposed to identify potential novel biomarkers and, ultimately, therapeutic targets.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDS |
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| |
| control | age-matched healthy persons |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Next Generation Sequencing | Diagnostic Test | Sequencing of patient samples will be performed in the facilities of ZIMCL. Following DNA extraction, the sequencing of granulocytes as well as of lymphocytes (control) will be carried out. IN addition to whole exome sequencing, a panel from SOPHIA GENETICS (which is also available for routine diagnostics) will be applied including the following MDS specific genes: ASXL1, BRAF, CBL, CEBPA, CSF3R, DNMT3A, EZH2, FLT3, HRAS, IDH1, IDH2, KRAS, MPL, NPM1, NRAS, RUNX1, SF3B1, SRSF2, TET2, TP53, U2AF1, WT1, ZRSR. Each patient sample will be "bulk sequenced", meaning that relevant mutations are detected down to an allele frequency of 2%. |
| Measure | Description | Time Frame |
|---|---|---|
| Definition of correlation between molecular aberrations and the sterile inflammatory tonus | baseline | |
| Definition how genetic aberrations and associated sterile inflammation impacts on health-related quality of life (HRQoL, e.g. fatigue) and functional activities in patients with MDS, MDS/MPN, or CHIP/CCUS | baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Definition of correlation of sterile inflammatory tonus with clinical variables (e.g. progression to secondary acute myeloid leukemia (sAML), complications (e.g. infections), and survival) | baseline |
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Inclusion Criteria:
Exclusion Criteria:
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MDS, MDS/MPN diagnosis based on current WHO classification. CCUS and CHIP defined by Valent (Valent, Oncotarget, 2018) and by Stauder (Stauder, Blood, 2018)
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Domink Wolf, Univ.Prof. | Contact | 0043512504 | 24003 | dominik.wolf@i-med.ac.at |
| Verena Petzer, MD | Contact | 0043512504 | 82979 |
| Name | Affiliation | Role |
|---|---|---|
| Domink Wolf, Univ.Prof. | Medical University Innsbruck | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of Innsbruck | Recruiting | Innsbruck | Tyrol | 6020 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29292655 | Background | Valent P, Stauder R, Theurl I, Geissler K, Sliwa T, Sperr WR, Bettelheim P, Sill H, Pfeilstocker M. Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform. Expert Rev Hematol. 2018 Feb;11(2):109-116. doi: 10.1080/17474086.2018.1420473. Epub 2018 Jan 2. | |
| 29141943 |
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Presentation at conferences and publication in a peer-reviewed journal
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|
| Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reaction | Diagnostic Test | Inflammasome activation is quantified by analyses of inflammasome-associated cytokine patterns. Multiplex assays for the quantification of the inflammasome-specific cytokines will be done from serum as well as from supernatants the stimulated blood cells. Cytokine quantification is carried out with Luminex FlexMap 3D. Serum cytokine levels will be quantitated in parallel. Quantification of RNA expression levels of inflammasome-related gene products will be performed by qPCRs from unstimulated and stimulated (=cryotube) blood cells. The necessary RNA extraction will be performed using a RNA extraction kit. |
|
| flow cytometry | Diagnostic Test | A detailed evaluation of the individual immune status is being conducted by the analysis of two specialized panels: Panel A provides a broad overview over various immune cell populations, while Panel B identifies T-cell sup-populations. |
|
| Metagenomics of stool samples | Diagnostic Test | DNA will be extracted from frozen fecal samples applying a bead-beating method using a GNOME DNA Isolation Kit (MP Biomedicals). DNA quality will be assessed using an Agilent 4200 TapeStation (Agilent Technologies). After final precipitation, DNA samples will be re-suspended in TE buffer and stored at -80 °C for further sequencing analysis. To this end, sequencing libraries will be generated using a Nextera XT DNA Sample Prep Kit (Illumina). Library quality will be confirmed using an Agilent 4200 TapeStation. Whole-genome shotgun sequencing of fecal samples will be carried out on a HiSeq2500 platform (Illumina). |
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| Clinical/demographic data | Diagnostic Test | Demographic and clinical data include: age, age at initial diagnosis, sex, diagnosis, actual comorbidities, medication at inclusion in study, cytogenetic and molecular profiles and standard laboratory parameters (blood count, differential leukocyte count, biochemistry, iron status, inflammatory markers like CRP, albumin, fibrinogen). |
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| Elicitation of the HRQoL | Other | Evaluation of HRQOL, of functional activities and of performance status will be done by the patient and/or the physician using validated scores. |
|
| Stauder R, Valent P, Theurl I. Anemia at older age: etiologies, clinical implications, and management. Blood. 2018 Feb 1;131(5):505-514. doi: 10.1182/blood-2017-07-746446. Epub 2017 Nov 15. |
| 37263977 | Derived | Loacker L, Petzer V, Bachmann S, Griesmacher A, Wolf D, Stauder R. High concordance of clone detection between peripheral blood and bone marrow by targeted next-generation sequencing-A pilot study in patients with MDS. Br J Haematol. 2023 Aug;202(3):e16-e19. doi: 10.1111/bjh.18889. Epub 2023 Jun 1. No abstract available. |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D000740 | Anemia |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D005434 | Flow Cytometry |
| ID | Term |
|---|---|
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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