Contributions
Abstract: PB1918
Type: Publication Only
Background
Myeloid-derived suppressor cells (MDSC) represent phenotypically heterogeneous populations of myeloid cells at different stages of maturation, which are able to suppress tumor-specific T cell response. MDSC are produced from normal granulocytic precursors in emergent states such as carcinoma and inflammation. Increases in MDSC have been reported in several hematologic malignancies including plasma cell myeloma, chronic lymphocytic leukemia, and acute myeloid leukemia.
Aims
This is a prospective study that measured frequencies of MDSC and we evaluated the significance and disease correlation of MDSC in patients with chronic myeloid leukemia (CML).
Methods
Peripheral blood (PB) (n=77) and bone marrow (BM) (n=76) aspirates were obtained from 6 pediatric and 60 adult patients diagnosed with CML. The status of CML included chronic (n=30), accelerated (n=3), blastic phases (n=4), and complete hematologic response (CHR) after treatment (n=40). A total of 40 PB samples were collected from age and sex-matched healthy controls (HC). Thirty eight patients who underwent staging work-up of lymphoma, but without BM involvement, were recruited for BM negative controls (NC). We measured the number of MDSC by flow cytometry using the FACSCanto II flow cytometer and FacsDIVA software (Becton-Dickinson Inc, CA, USA). We acquired 50,000 cells and quantified the frequencies of 2 subsets of MDSC, granulocytic MDSC (gMDSC, HLA-DRlowCD11b+CD14−CD33+CD15+) and monocytic MDSC (mMDSC, HLA-DRlowCD11b+CD14+) in PB and BM.
Results
The correlation between BM-gMDSC% and PB-gMDSC% was good (r=0.712, P<0.001) and BM-gMDSC% was linear to PB-gMDSC% (y=0.960x+4.101, r²=0.507). BM-gMDSC% and PB-gMDSC% showed negative correlation with BCR-ABL1 quantitation (r=−0.478 and r=−0.547, P<0.001, respectively). BM-gMDSC% at diagnosis (mean±SD; 5.8±13.8%) were significantly lower than that of the CHR (40.6±16.4%) and BM NC group (37.8±11.3 %) (P<0.001, respectively) (Fig.1). BM-gMDSC% was lower in the BCR-ABL1 positive CHR group (23.4±18.3%) as compared to the BCR-ABL1 negative CHR group (31.4±14.1%), but not statistically significant (P=0.123). PB-gMDSC% at diagnosis (8.7±14.4%) was also significantly lower than that of the CHR (22.8±11.2%) and HC groups (27.7±10.9%) (P<0.001, respectively). However, there was no statistical difference in the mMDSC% in both BM and PB. The overall survival rate of the high BM-gMDSC% group (≥20%) was higher than that of the low BM-gMDSC% group (<20%) in both diagnosis and CHR groups (P=0.430 and P=0.011, respectively). However, both BM-mMDSC% and PB-mMDSC% did not show significant differences between each group.
Conclusion
BM-gMDSC% and PB-gMDSC% at diagnosis were significantly lower than those of BM NC and HC, respectively. Higher gMDSC% at CHR might be related to good prognosis in CML patients. These findings are contrary to the known MDSC findings in other malignancies. Granulocytes in CML are differentiated from leukemic stem cells, and probably the emergent myelopoietic condition does not affect the granulopoiesis of CML. The increased MDSC in CHR might reflect the regeneration of normal granulopoietic precursors.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, flow cytometry, prognosis
Abstract: PB1918
Type: Publication Only
Background
Myeloid-derived suppressor cells (MDSC) represent phenotypically heterogeneous populations of myeloid cells at different stages of maturation, which are able to suppress tumor-specific T cell response. MDSC are produced from normal granulocytic precursors in emergent states such as carcinoma and inflammation. Increases in MDSC have been reported in several hematologic malignancies including plasma cell myeloma, chronic lymphocytic leukemia, and acute myeloid leukemia.
Aims
This is a prospective study that measured frequencies of MDSC and we evaluated the significance and disease correlation of MDSC in patients with chronic myeloid leukemia (CML).
Methods
Peripheral blood (PB) (n=77) and bone marrow (BM) (n=76) aspirates were obtained from 6 pediatric and 60 adult patients diagnosed with CML. The status of CML included chronic (n=30), accelerated (n=3), blastic phases (n=4), and complete hematologic response (CHR) after treatment (n=40). A total of 40 PB samples were collected from age and sex-matched healthy controls (HC). Thirty eight patients who underwent staging work-up of lymphoma, but without BM involvement, were recruited for BM negative controls (NC). We measured the number of MDSC by flow cytometry using the FACSCanto II flow cytometer and FacsDIVA software (Becton-Dickinson Inc, CA, USA). We acquired 50,000 cells and quantified the frequencies of 2 subsets of MDSC, granulocytic MDSC (gMDSC, HLA-DRlowCD11b+CD14−CD33+CD15+) and monocytic MDSC (mMDSC, HLA-DRlowCD11b+CD14+) in PB and BM.
Results
The correlation between BM-gMDSC% and PB-gMDSC% was good (r=0.712, P<0.001) and BM-gMDSC% was linear to PB-gMDSC% (y=0.960x+4.101, r²=0.507). BM-gMDSC% and PB-gMDSC% showed negative correlation with BCR-ABL1 quantitation (r=−0.478 and r=−0.547, P<0.001, respectively). BM-gMDSC% at diagnosis (mean±SD; 5.8±13.8%) were significantly lower than that of the CHR (40.6±16.4%) and BM NC group (37.8±11.3 %) (P<0.001, respectively) (Fig.1). BM-gMDSC% was lower in the BCR-ABL1 positive CHR group (23.4±18.3%) as compared to the BCR-ABL1 negative CHR group (31.4±14.1%), but not statistically significant (P=0.123). PB-gMDSC% at diagnosis (8.7±14.4%) was also significantly lower than that of the CHR (22.8±11.2%) and HC groups (27.7±10.9%) (P<0.001, respectively). However, there was no statistical difference in the mMDSC% in both BM and PB. The overall survival rate of the high BM-gMDSC% group (≥20%) was higher than that of the low BM-gMDSC% group (<20%) in both diagnosis and CHR groups (P=0.430 and P=0.011, respectively). However, both BM-mMDSC% and PB-mMDSC% did not show significant differences between each group.
Conclusion
BM-gMDSC% and PB-gMDSC% at diagnosis were significantly lower than those of BM NC and HC, respectively. Higher gMDSC% at CHR might be related to good prognosis in CML patients. These findings are contrary to the known MDSC findings in other malignancies. Granulocytes in CML are differentiated from leukemic stem cells, and probably the emergent myelopoietic condition does not affect the granulopoiesis of CML. The increased MDSC in CHR might reflect the regeneration of normal granulopoietic precursors.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, flow cytometry, prognosis