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Myelodysplastic syndrome (MDS) is a highly heterogeneous clonal hematopoietic disorder. Allogeneic stem cell transplantation (HSCT) remains the only curative treatment, and is of particular interest in patients at high risk for progression to acute myeloid leukemia (AML). In MDS, CD34+/CD38- cells possess MDS stem cell potential and secondary AML (sAML) clones originate from MDS disease stage. However, the prognostic impact of the pre-treatment stem cell population burden in MDS remains unknown. We retrospectively analyzed the prognostic impact of the pre-treatment CD34+/CD38- cell burden in 124 MDS patients who received allogeneic HSCT at our institution. A high pre-treatment bone marrow CD34+/CD38- cell burden (≥1%) associated with worse genetic risk and a higher incidence of blast excess. Patients with a high CD34+/CD38- cell burden had a significantly higher cumulative incidence of MDS relapse (CIR), a higher cumulative incidence of secondary AML and a trend for shorter overall survival after allogeneic HSCT. In multivariable analyses, this prognostic impact was shown to be independent of other clinical and cytogenetic risk factors in MDS. Patients suffering MDS relapse or progression to AML also had a higher pre-treatment CD34±/CD38- cell burden as continuous variable. The observed prognostic impact is likely mediated by MDS stem cells within the CD34+/CD38- cell population initiating MDS relapse or progression to AML. New therapeutic strategies targeting MDS stem cells might improve outcomes.
This article was published in the following journal.
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A member of the prominin family, AC133 Antigen is a 5-transmembrane antigen occurring as several isoforms produced by alternative splicing which are processed into mature forms. In humans, it is expressed as a subset of CD34 (bright) human hematopoietic stem cells and CD34 positive leukemias. Functionally, it is associated with roles in cell differentiation, proliferation, and apoptosis. Specifically, it regulates the organization of apical plasma membrane in epithelial cells, disk morphogenesis during early retinal development, MAPK and Akt signaling pathways, and in cholesterol metabolism.
Measure of the burden of disease using the disability-adjusted-life-year (DALY). This time-based measure combines years of life lost due to premature mortality and years of life lost due to time lived in states of less than full health. The metric was developed to assess the burden of disease consistently across diseases, risk factors and regions.
The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.
A morpholine and thiophene derivative that functions as a FACTOR XA INHIBITOR and is used in the treatment and prevention of DEEP-VEIN THROMBOSIS and PULMONARY EMBOLISM. It is also used for the prevention of STROKE and systemic embolization in patients with non-valvular ATRIAL FIBRILLATION, and for the prevention of atherothrombotic events in patients after an ACUTE CORONARY SYNDROME.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
Track and monitor developments in stem cell research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry. BioPort...
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...