Contributions
Abstract: EP490
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Acute myeloid leukemia (AML) is the most common malignant of the hematopoietic system. Allogeneic hematopoietic stem cell transplantation not only improves the prognosis of patients, but also emphasizes the role of immunity in the development of AML. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cell populations derived from myeloid cells, However, their role in AML has not been extensively elucidated in bone marrow (BM) or peripheral blood (PB). Furthermore, it remains unclear whether the percentage of MDSCs derived from BM and PB of patients with AML are consistent. Extracellular vesicles (EVs) as mediator in intercellular communication and play an important role in tumor immunity. However, the role of EVs derived from AML (AML-EVs) in MDSCs expansion is not well understood.
Aims
This study aimed to investigate the role of MDSCs in patients with newly diagnosed AMLand evaluate the role of extracellular vesicle-induced MDSCs in AML.
Methods
Collected BM or PB from newly diagnosed AML patients and healthy donors (HD) to extract mononuclear cells (MNCs), and the percentage of MDSCs and its subpopulation was determined by flow cytometry. Analyzed the relationship between MDSCs and clinicopathological characters, MICM classification, survival. In addition, extracted and identified the EVs in the serums from HDs and AML patients. AML-EVs and HD-EVs were incubated with peripheral blood mononuclear cells (PBMCs) or MNCs from hematopoietic stem cell (HSCs) suspension. And the percentage of MDSCs were detected by flow cytometry.
Results
The MDSCs and its subpopulation percentage was significantly higher in patients with AML than in HDs, with no significant difference between PB and BM. The MDSCs percentage in AML patients was positively correlated with WBC, β-MG, LDH, ferritin, and negatively correlated with PLT. However, MDSCs percentage was not correlated with RBC, HGB, PB blasts cells and BM blasts cells. The MDSCs percentage was positively correlated with AML risk stratification which the higher risk displayed the elevated MDSCs. The MDSCs percentage varied among those with different fusion genes and gene mutations, with higher frequency observed in those with FLT3- ITD mutation and NUP98- HOXA9 fusion genes. The MDSCs percentage at the time of diagnosis was not significant different among the CR, PR, and NR groups, and was also no significantly differ between the MRD positive and negative group. Further categorized into low- and high-MDSC groups based on the median MDSCs percentage of 3.07% at the time of diagnosis, and the OS was significantly longer in the low-MDSC group than in the high-MDSC group. EVs entered into MNCs was observed by fluorescence microscopy. The MDSCs frequency was significantly higher in myeloid cells incubated with AML-EVs, but the MDSCs frequency was no significant change in PBMCs incubated with AML-EVs.
Conclusion
The MDSCs percentage was significantly elevated in both the BM and PB of AML patients, and there was no statistical difference in PB and BM. The percentage of MDSCs was positively correlated with AML risk stratification which the higher risk displayed the elevated MDSCs. The OS was significantly longer in the low-MDSCs group than in the high-MDSCs group. Taken together, MDSCs level at the time of diagnosis could predict AML prognosis. AML-EVs could promote the transformation of myeloid cells into MDSCs, and the role of AML-EVs in inducing MDSCs was stronger in myeloid cells than in PBMCs.
Keyword(s): Acute myeloid leukemia, Cellular immunity, Clinical data
Abstract: EP490
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Acute myeloid leukemia (AML) is the most common malignant of the hematopoietic system. Allogeneic hematopoietic stem cell transplantation not only improves the prognosis of patients, but also emphasizes the role of immunity in the development of AML. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cell populations derived from myeloid cells, However, their role in AML has not been extensively elucidated in bone marrow (BM) or peripheral blood (PB). Furthermore, it remains unclear whether the percentage of MDSCs derived from BM and PB of patients with AML are consistent. Extracellular vesicles (EVs) as mediator in intercellular communication and play an important role in tumor immunity. However, the role of EVs derived from AML (AML-EVs) in MDSCs expansion is not well understood.
Aims
This study aimed to investigate the role of MDSCs in patients with newly diagnosed AMLand evaluate the role of extracellular vesicle-induced MDSCs in AML.
Methods
Collected BM or PB from newly diagnosed AML patients and healthy donors (HD) to extract mononuclear cells (MNCs), and the percentage of MDSCs and its subpopulation was determined by flow cytometry. Analyzed the relationship between MDSCs and clinicopathological characters, MICM classification, survival. In addition, extracted and identified the EVs in the serums from HDs and AML patients. AML-EVs and HD-EVs were incubated with peripheral blood mononuclear cells (PBMCs) or MNCs from hematopoietic stem cell (HSCs) suspension. And the percentage of MDSCs were detected by flow cytometry.
Results
The MDSCs and its subpopulation percentage was significantly higher in patients with AML than in HDs, with no significant difference between PB and BM. The MDSCs percentage in AML patients was positively correlated with WBC, β-MG, LDH, ferritin, and negatively correlated with PLT. However, MDSCs percentage was not correlated with RBC, HGB, PB blasts cells and BM blasts cells. The MDSCs percentage was positively correlated with AML risk stratification which the higher risk displayed the elevated MDSCs. The MDSCs percentage varied among those with different fusion genes and gene mutations, with higher frequency observed in those with FLT3- ITD mutation and NUP98- HOXA9 fusion genes. The MDSCs percentage at the time of diagnosis was not significant different among the CR, PR, and NR groups, and was also no significantly differ between the MRD positive and negative group. Further categorized into low- and high-MDSC groups based on the median MDSCs percentage of 3.07% at the time of diagnosis, and the OS was significantly longer in the low-MDSC group than in the high-MDSC group. EVs entered into MNCs was observed by fluorescence microscopy. The MDSCs frequency was significantly higher in myeloid cells incubated with AML-EVs, but the MDSCs frequency was no significant change in PBMCs incubated with AML-EVs.
Conclusion
The MDSCs percentage was significantly elevated in both the BM and PB of AML patients, and there was no statistical difference in PB and BM. The percentage of MDSCs was positively correlated with AML risk stratification which the higher risk displayed the elevated MDSCs. The OS was significantly longer in the low-MDSCs group than in the high-MDSCs group. Taken together, MDSCs level at the time of diagnosis could predict AML prognosis. AML-EVs could promote the transformation of myeloid cells into MDSCs, and the role of AML-EVs in inducing MDSCs was stronger in myeloid cells than in PBMCs.
Keyword(s): Acute myeloid leukemia, Cellular immunity, Clinical data