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MONUCLEAR MYELOID-DERIVED SUPPRESSOR CELLS (MO-MDSC) EXPANSION AND PROGRESSION IN MYELODYSPLASTIC SYNDROMES
Author(s): ,
Francisca Hernández Mohedo
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
,
Paola Montes Ramos
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
,
Sara Maroto Gallego
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
,
Antonio Cruz Díaz
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
,
Elena Espinosa de los Monteros
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
,
Manuel Jurado Chacón
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
,
Francisco Ruiz Cabello
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
Pilar Jiménez Gámiz
Affiliations:
Hematology,Complejo Hospitalario Universitario de Granada,Granada,Spain
(Abstract release date: 05/19/16) EHA Library. Hernandez Mohedo F. 06/09/16; 132749; E1200 Disclosure(s): I have disclosed any relationship with corporate organizations, such as grant/research support, stock shareholder, honorariums, consultant work
Dr. Francisca Hernandez Mohedo
Dr. Francisca Hernandez Mohedo
Contributions
Abstract
Abstract: E1200

Type: Eposter Presentation

Background
Myeloid Derived Suppressor Cells” (MDSC) are a heterogeneous population of inmature myeloid cells constituent of bone marrow microenvironment, whose expansion hampers the host anti-tumor immune response. They can play a pathogenetic role in the development of ineffective hematopoiesis in myelodysplastic síndromes (MDS), and contribute to progression to acute myeloid leukemia (AML), through inmunotolerance and  as a cellular effectors that suppress hematopoiesis. The mechanisms that determine the evolution to AML are not entirely clarified although, a role of the immune response has been suggested. In this sense, the bone marrow microenvironment expansion of suppressor cells of monocytic origin (Mo-MDSC) and T cell inmunosupressive efector (Tregs) can contribute to tumor progression.

Aims
Our aim has been to investigate a possible role of the myeloid supressor cells of monocytic origin (CD14+HLA-DRlow/-) and Tregs in the development of ineffective hematopoiesis in myelodysplastic síndromes (MDS), that may contribute to the development and progression to acute myeloid leukemia (AML) of MDS.  

Methods
We performed a prospective analysis of a group of 31 patients with MDS and AML evolved from MDS and a control group of 40 healthy subjects. It was analyzed by multiparametric flow cytometry techniques to study the presence of MDSC-Mo (CD14+HLA-DRlow/-) cells and CD34 + blasts, in peripheral blood and bone marrow in both MDS patients and control cases. The monoclonal antibodies marked with their respective fluorochromes were: CD45-V500, CD3-V450,. CD4-PER, CD8-APH- 7, CD19-PE-CY7, CD56-PE-CY7, CD127-APC, CD34-APC, CD64-FICT, DR- V450, CD25-PE-CY7, CD14-PE and CD64-FICT and  anti DR-V450.The clinical and biological profile of MDS and control group has analyzed with statistical software IBM SPSS.19.

Results
In the 31 peripheral blood samples of patients with MDS and AML evolved from MDS, the WHO-2008 diagnostic classification was: RCUD(4), RCMD(8), RARS and RCMD-RS(2), RAEB-1(3), RAEB-2(6), MMCL-1(5) and AML evolved from MDS (3). We observed a positive correlation between MDSC cells with phenotype CD14+ HLA-DRlow/- and CD34 + blasts in peripheral blood (p=0,001). In addition, the frequency of expression of CD14+ HLA-DRlow/- cells, was significantly elevated in MDS patients as compared to the control cases (26,52+/-5,47 vs 6,66+/-1,06; p=0,014). No significant results were obtained in bone marrow for the studied subpopulations. With regard to WHO classification, we observed a higher value of MDSC in RAEB-2 and AML vs other MDS, almost statisticaly significant (45,40+/-12,70 vs 18,80+/-5,04; p=0.055). The analysis of prognostic scoring system IPSS y IPSS-R shows higher incidence of Mo-MDSC in High risk IPSS (High + Int-2 vs Int-1 and Low risk) (59,55+/-14,14 vs 15,12+/-3,61; p=0.004) and High risk IPSS-R (Very High, High and Int vs Low and very low risk)(37,06+/-7,99 vs 9,49+/-4,05; p=0.006). Increase frequency of Mo- MDSCs was also linked to poor and intermediate cytogenetic risks (59,55+/-14,14 vs 15,10+/-3,94; Poor and Int vs Good and Very good; p=0.006).

Conclusion
The expansion of cells with MDSCs phenotype of monocytic origin can suppose a higher risk in  myelodysplastic syndromes transformation, favouring the immune escape, which may be important for understand the pathogenesis of high-risk MDS and with poor cytogenetic risks. The good correlation between myeloid supressor cells of monocytic origin (CD14+HLA-DRlow/-) and CD34 + blasts in peripheral blood, allows monitoring of patients with MDS.

Session topic: E-poster

Keyword(s): MDS/AML, Microenvironment, Myelodysplasia
Abstract: E1200

Type: Eposter Presentation

Background
Myeloid Derived Suppressor Cells” (MDSC) are a heterogeneous population of inmature myeloid cells constituent of bone marrow microenvironment, whose expansion hampers the host anti-tumor immune response. They can play a pathogenetic role in the development of ineffective hematopoiesis in myelodysplastic síndromes (MDS), and contribute to progression to acute myeloid leukemia (AML), through inmunotolerance and  as a cellular effectors that suppress hematopoiesis. The mechanisms that determine the evolution to AML are not entirely clarified although, a role of the immune response has been suggested. In this sense, the bone marrow microenvironment expansion of suppressor cells of monocytic origin (Mo-MDSC) and T cell inmunosupressive efector (Tregs) can contribute to tumor progression.

Aims
Our aim has been to investigate a possible role of the myeloid supressor cells of monocytic origin (CD14+HLA-DRlow/-) and Tregs in the development of ineffective hematopoiesis in myelodysplastic síndromes (MDS), that may contribute to the development and progression to acute myeloid leukemia (AML) of MDS.  

Methods
We performed a prospective analysis of a group of 31 patients with MDS and AML evolved from MDS and a control group of 40 healthy subjects. It was analyzed by multiparametric flow cytometry techniques to study the presence of MDSC-Mo (CD14+HLA-DRlow/-) cells and CD34 + blasts, in peripheral blood and bone marrow in both MDS patients and control cases. The monoclonal antibodies marked with their respective fluorochromes were: CD45-V500, CD3-V450,. CD4-PER, CD8-APH- 7, CD19-PE-CY7, CD56-PE-CY7, CD127-APC, CD34-APC, CD64-FICT, DR- V450, CD25-PE-CY7, CD14-PE and CD64-FICT and  anti DR-V450.The clinical and biological profile of MDS and control group has analyzed with statistical software IBM SPSS.19.

Results
In the 31 peripheral blood samples of patients with MDS and AML evolved from MDS, the WHO-2008 diagnostic classification was: RCUD(4), RCMD(8), RARS and RCMD-RS(2), RAEB-1(3), RAEB-2(6), MMCL-1(5) and AML evolved from MDS (3). We observed a positive correlation between MDSC cells with phenotype CD14+ HLA-DRlow/- and CD34 + blasts in peripheral blood (p=0,001). In addition, the frequency of expression of CD14+ HLA-DRlow/- cells, was significantly elevated in MDS patients as compared to the control cases (26,52+/-5,47 vs 6,66+/-1,06; p=0,014). No significant results were obtained in bone marrow for the studied subpopulations. With regard to WHO classification, we observed a higher value of MDSC in RAEB-2 and AML vs other MDS, almost statisticaly significant (45,40+/-12,70 vs 18,80+/-5,04; p=0.055). The analysis of prognostic scoring system IPSS y IPSS-R shows higher incidence of Mo-MDSC in High risk IPSS (High + Int-2 vs Int-1 and Low risk) (59,55+/-14,14 vs 15,12+/-3,61; p=0.004) and High risk IPSS-R (Very High, High and Int vs Low and very low risk)(37,06+/-7,99 vs 9,49+/-4,05; p=0.006). Increase frequency of Mo- MDSCs was also linked to poor and intermediate cytogenetic risks (59,55+/-14,14 vs 15,10+/-3,94; Poor and Int vs Good and Very good; p=0.006).

Conclusion
The expansion of cells with MDSCs phenotype of monocytic origin can suppose a higher risk in  myelodysplastic syndromes transformation, favouring the immune escape, which may be important for understand the pathogenesis of high-risk MDS and with poor cytogenetic risks. The good correlation between myeloid supressor cells of monocytic origin (CD14+HLA-DRlow/-) and CD34 + blasts in peripheral blood, allows monitoring of patients with MDS.

Session topic: E-poster

Keyword(s): MDS/AML, Microenvironment, Myelodysplasia

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