Contributions
Abstract: PB1612
Type: Publication Only
Session title: Myelodysplastic syndromes - Biology & Translational Research
Background
Refinement of prognosis is crucial for improvement of outcome in patients with myelodyslastic syndrome (MDS). Flow cytometry and molecular genetics can be used for this purpose.
Aims
In our study we tried to combine these two approaches to define subgroups of MDS patients with different clinical course.
Methods
We performed flow cytometry to quantitatively assess T- and NK-cells, myeloid progenitors, T-regulators, myeloid-derived suppressor cells in bone marrow of 38 adult MDS patients after signing informed consent for participation in research. In each cell population we measured expression of PD-1, PD-L1, PD-L2, CD80, CTLA-4, LAG3, TIM3, ICOS-L. In 23 patients we carried out Sanger sequencing of SF3B1, DNMT3A, RUNX1, ASXL1, TP53 genes. We tracked the 2-year outcome of the included patients regarding the defined flow and molecular parameters. This work was supported by Russian Science Foundation, grant №17-75-20145-П.
Results
We observed significant role of PD-L1 expressing regulatory T-cells (PDL1-Tregs) subpopulation level. Patients with PDL1-Tregs higher than 0.003% of all nucleated cells showed lower 2-year overall (OS2) and relapse-free (RFS2) survival (41.3% and 35.8% vs. 85.7% and 85.7% in those with PDL1-Tregs lower than 0.003%, respectively, p<0.05). The number of mutations significantly influenced OS2 (80%, 60%, and 0% for 0, 1, and 2 mutations, respectively, p<0.05) and RFS2 (72.2%, 60%, and 0% for 0, 1, and 2 mutations, respectively, p<0.05). When combining these results we managed to derive the compound index consisting of two binary variables: PDL1-Tregs higher or lower than 0.003% of all nucleated cells and presence or absence of at least one molecular mutation obtaining 4 subgroups of MDS patients with significantly different OS2 and RFS2. Thus, in lower PDL1-Tregs without mutations, lower PDL1-Tregs with mutations, higher PDL1-Tregs without mutations, and higher PDL1-Tregs with mutations OS2 was 100%, 50%, 72%, and 0% (p<0.05), respectively, and RFS2 was 100%, 50%, 80%, and 0% (p<0.05), respectively.
Conclusion
Our preliminary results underline the importance of using parallel approaches and new methods for prognosis in MDS patients. Further studies are warranted.
Keyword(s): Flow cytometry, Molecular markers, Myelodysplasia, Prognosis
Abstract: PB1612
Type: Publication Only
Session title: Myelodysplastic syndromes - Biology & Translational Research
Background
Refinement of prognosis is crucial for improvement of outcome in patients with myelodyslastic syndrome (MDS). Flow cytometry and molecular genetics can be used for this purpose.
Aims
In our study we tried to combine these two approaches to define subgroups of MDS patients with different clinical course.
Methods
We performed flow cytometry to quantitatively assess T- and NK-cells, myeloid progenitors, T-regulators, myeloid-derived suppressor cells in bone marrow of 38 adult MDS patients after signing informed consent for participation in research. In each cell population we measured expression of PD-1, PD-L1, PD-L2, CD80, CTLA-4, LAG3, TIM3, ICOS-L. In 23 patients we carried out Sanger sequencing of SF3B1, DNMT3A, RUNX1, ASXL1, TP53 genes. We tracked the 2-year outcome of the included patients regarding the defined flow and molecular parameters. This work was supported by Russian Science Foundation, grant №17-75-20145-П.
Results
We observed significant role of PD-L1 expressing regulatory T-cells (PDL1-Tregs) subpopulation level. Patients with PDL1-Tregs higher than 0.003% of all nucleated cells showed lower 2-year overall (OS2) and relapse-free (RFS2) survival (41.3% and 35.8% vs. 85.7% and 85.7% in those with PDL1-Tregs lower than 0.003%, respectively, p<0.05). The number of mutations significantly influenced OS2 (80%, 60%, and 0% for 0, 1, and 2 mutations, respectively, p<0.05) and RFS2 (72.2%, 60%, and 0% for 0, 1, and 2 mutations, respectively, p<0.05). When combining these results we managed to derive the compound index consisting of two binary variables: PDL1-Tregs higher or lower than 0.003% of all nucleated cells and presence or absence of at least one molecular mutation obtaining 4 subgroups of MDS patients with significantly different OS2 and RFS2. Thus, in lower PDL1-Tregs without mutations, lower PDL1-Tregs with mutations, higher PDL1-Tregs without mutations, and higher PDL1-Tregs with mutations OS2 was 100%, 50%, 72%, and 0% (p<0.05), respectively, and RFS2 was 100%, 50%, 80%, and 0% (p<0.05), respectively.
Conclusion
Our preliminary results underline the importance of using parallel approaches and new methods for prognosis in MDS patients. Further studies are warranted.
Keyword(s): Flow cytometry, Molecular markers, Myelodysplasia, Prognosis