PDCD1 EXPRESSION AND SNP ANALYSES IN AML, MDS AND S-AML PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Zaleska J. 06/09/16; 134529; PB1629
Ms. Joanna Zaleska
Contributions
Contributions
Abstract
Abstract: PB1629
Type: Publication Only
Background
One of the potential mechanism responsible for evading cytotoxic T lymphocytes by tumor cells might be the programmed death-1 receptor (PD-1) signaling pathway. PD-1 and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, promoting tumor development. Recent findings showed elevated expression of PD-1 and PD-L1 on CD34+ cells in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients suggesting that deregulation of PD-1/PD-L1 axis may contribute the MDS pathogenesis. Moreover, in patients treated with epigenetic therapy PD-L1 and PD-1 expression was upregulated indicating that induction of PD-1 and PD-1 ligands may be involved in hypomethylating agents (HMAs) resistance. PDCD1 polymorphisms are associated with susceptibility to several types of cancer.
Aims
We aim to characterize the PDCD1 expression and six PDCD1 polymorphisms in AML, MDS and s-AML patients samples as well as determine whether expression of PD-1 in those patients is driven by the genetic background.
Methods
PDCD1 mRNA expression was assessed in bone marrow mononuclear cells (BMMC) of 62 MDS, 54 AML and 8 s-AML patients samples using qRT-PCR method. Six SNP for PD-1 that demonstrate relevant associations with a higher risk of developing autoimmune diseases were assessed in AML, MDS and s-AML patients as well as 100 healthy volunteers (HVs): PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.6 (rs10204525), PD -1.7 (rs41386349), PD-1.9 (rs2227982). Moreover, immunohistochemical (IHC) stainings of 12 AML and 8 MDS bone marrow smears for PD-1 protein were performed.
Results
We observed significant decreased PDCD1 expression in AML group compared to HVs and MDS, (median: 0.0001 vs 0.0003, p<0.001 and 0.0001 vs 0.0003, p<0.001) but no differences in MDS and s-AML groups compared to HVs. IHC stainings showed PD-1 expression on blast cells in 6/12 AML and 6/8 MDS cases ranging from 1-92%. AML patients were stratified into three genetic groups according to prognosis: favorable risk, intermediate I risk and intermediate II / adverse risk and PDCD1 expression was compared between these groups. No significant differences were found between these groups. MDS patients were divided according to IPSS scoring systems into two groups: first with IPSS ranging from 0.0 to 0.5 and second with IPSS from 1 to 3. No significant difference were observed between these groups in case of PDCD1 expression (median: 0.0004 vs 0.0002, p=0.11). We observed significant differences in PDCD1 expression level regarding to PD-1.1.5 polymorphism. Moreover, analysis of a PD-1.1.3 polymorphism in HVs and MDS groups revealed that genotype GG was associated with nearly fivefold lower risk of disease (OR=4.93, p=0.009). We observed significant differences in OS in AML patients in case of presence of certain genotypes of PD-1.1.6. Genotype AA was significant associated with higher risk of shorter OS compared to the rest of the genotypes (58 vs 333 days, HR=35; p=0.0188).
Conclusion
We found significant differences in PDCD1 expression in AML and MDS patients that might indicate deregulation of a signal transduction through the PD-1/PD-L1 axis. By IHC stainings we were able to determine PD-1 expression on blast cells in 6/12 AML and 6/8 MDS bone marrow smears. Moreover, SNP analysis in AML patients revealed potential prognostic impact of PD-1.1.6 polymorphism.This work was supported by National Centre for Science Grant HARMONIA (UMO-2013/10/M/NZ5/00313).
Session topic: E-poster
Keyword(s): AML, MDS, Polymorphism
Type: Publication Only
Background
One of the potential mechanism responsible for evading cytotoxic T lymphocytes by tumor cells might be the programmed death-1 receptor (PD-1) signaling pathway. PD-1 and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, promoting tumor development. Recent findings showed elevated expression of PD-1 and PD-L1 on CD34+ cells in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients suggesting that deregulation of PD-1/PD-L1 axis may contribute the MDS pathogenesis. Moreover, in patients treated with epigenetic therapy PD-L1 and PD-1 expression was upregulated indicating that induction of PD-1 and PD-1 ligands may be involved in hypomethylating agents (HMAs) resistance. PDCD1 polymorphisms are associated with susceptibility to several types of cancer.
Aims
We aim to characterize the PDCD1 expression and six PDCD1 polymorphisms in AML, MDS and s-AML patients samples as well as determine whether expression of PD-1 in those patients is driven by the genetic background.
Methods
PDCD1 mRNA expression was assessed in bone marrow mononuclear cells (BMMC) of 62 MDS, 54 AML and 8 s-AML patients samples using qRT-PCR method. Six SNP for PD-1 that demonstrate relevant associations with a higher risk of developing autoimmune diseases were assessed in AML, MDS and s-AML patients as well as 100 healthy volunteers (HVs): PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.6 (rs10204525), PD -1.7 (rs41386349), PD-1.9 (rs2227982). Moreover, immunohistochemical (IHC) stainings of 12 AML and 8 MDS bone marrow smears for PD-1 protein were performed.
Results
We observed significant decreased PDCD1 expression in AML group compared to HVs and MDS, (median: 0.0001 vs 0.0003, p<0.001 and 0.0001 vs 0.0003, p<0.001) but no differences in MDS and s-AML groups compared to HVs. IHC stainings showed PD-1 expression on blast cells in 6/12 AML and 6/8 MDS cases ranging from 1-92%. AML patients were stratified into three genetic groups according to prognosis: favorable risk, intermediate I risk and intermediate II / adverse risk and PDCD1 expression was compared between these groups. No significant differences were found between these groups. MDS patients were divided according to IPSS scoring systems into two groups: first with IPSS ranging from 0.0 to 0.5 and second with IPSS from 1 to 3. No significant difference were observed between these groups in case of PDCD1 expression (median: 0.0004 vs 0.0002, p=0.11). We observed significant differences in PDCD1 expression level regarding to PD-1.1.5 polymorphism. Moreover, analysis of a PD-1.1.3 polymorphism in HVs and MDS groups revealed that genotype GG was associated with nearly fivefold lower risk of disease (OR=4.93, p=0.009). We observed significant differences in OS in AML patients in case of presence of certain genotypes of PD-1.1.6. Genotype AA was significant associated with higher risk of shorter OS compared to the rest of the genotypes (58 vs 333 days, HR=35; p=0.0188).
Conclusion
We found significant differences in PDCD1 expression in AML and MDS patients that might indicate deregulation of a signal transduction through the PD-1/PD-L1 axis. By IHC stainings we were able to determine PD-1 expression on blast cells in 6/12 AML and 6/8 MDS bone marrow smears. Moreover, SNP analysis in AML patients revealed potential prognostic impact of PD-1.1.6 polymorphism.This work was supported by National Centre for Science Grant HARMONIA (UMO-2013/10/M/NZ5/00313).
Session topic: E-poster
Keyword(s): AML, MDS, Polymorphism
Abstract: PB1629
Type: Publication Only
Background
One of the potential mechanism responsible for evading cytotoxic T lymphocytes by tumor cells might be the programmed death-1 receptor (PD-1) signaling pathway. PD-1 and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, promoting tumor development. Recent findings showed elevated expression of PD-1 and PD-L1 on CD34+ cells in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients suggesting that deregulation of PD-1/PD-L1 axis may contribute the MDS pathogenesis. Moreover, in patients treated with epigenetic therapy PD-L1 and PD-1 expression was upregulated indicating that induction of PD-1 and PD-1 ligands may be involved in hypomethylating agents (HMAs) resistance. PDCD1 polymorphisms are associated with susceptibility to several types of cancer.
Aims
We aim to characterize the PDCD1 expression and six PDCD1 polymorphisms in AML, MDS and s-AML patients samples as well as determine whether expression of PD-1 in those patients is driven by the genetic background.
Methods
PDCD1 mRNA expression was assessed in bone marrow mononuclear cells (BMMC) of 62 MDS, 54 AML and 8 s-AML patients samples using qRT-PCR method. Six SNP for PD-1 that demonstrate relevant associations with a higher risk of developing autoimmune diseases were assessed in AML, MDS and s-AML patients as well as 100 healthy volunteers (HVs): PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.6 (rs10204525), PD -1.7 (rs41386349), PD-1.9 (rs2227982). Moreover, immunohistochemical (IHC) stainings of 12 AML and 8 MDS bone marrow smears for PD-1 protein were performed.
Results
We observed significant decreased PDCD1 expression in AML group compared to HVs and MDS, (median: 0.0001 vs 0.0003, p<0.001 and 0.0001 vs 0.0003, p<0.001) but no differences in MDS and s-AML groups compared to HVs. IHC stainings showed PD-1 expression on blast cells in 6/12 AML and 6/8 MDS cases ranging from 1-92%. AML patients were stratified into three genetic groups according to prognosis: favorable risk, intermediate I risk and intermediate II / adverse risk and PDCD1 expression was compared between these groups. No significant differences were found between these groups. MDS patients were divided according to IPSS scoring systems into two groups: first with IPSS ranging from 0.0 to 0.5 and second with IPSS from 1 to 3. No significant difference were observed between these groups in case of PDCD1 expression (median: 0.0004 vs 0.0002, p=0.11). We observed significant differences in PDCD1 expression level regarding to PD-1.1.5 polymorphism. Moreover, analysis of a PD-1.1.3 polymorphism in HVs and MDS groups revealed that genotype GG was associated with nearly fivefold lower risk of disease (OR=4.93, p=0.009). We observed significant differences in OS in AML patients in case of presence of certain genotypes of PD-1.1.6. Genotype AA was significant associated with higher risk of shorter OS compared to the rest of the genotypes (58 vs 333 days, HR=35; p=0.0188).
Conclusion
We found significant differences in PDCD1 expression in AML and MDS patients that might indicate deregulation of a signal transduction through the PD-1/PD-L1 axis. By IHC stainings we were able to determine PD-1 expression on blast cells in 6/12 AML and 6/8 MDS bone marrow smears. Moreover, SNP analysis in AML patients revealed potential prognostic impact of PD-1.1.6 polymorphism.This work was supported by National Centre for Science Grant HARMONIA (UMO-2013/10/M/NZ5/00313).
Session topic: E-poster
Keyword(s): AML, MDS, Polymorphism
Type: Publication Only
Background
One of the potential mechanism responsible for evading cytotoxic T lymphocytes by tumor cells might be the programmed death-1 receptor (PD-1) signaling pathway. PD-1 and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, promoting tumor development. Recent findings showed elevated expression of PD-1 and PD-L1 on CD34+ cells in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients suggesting that deregulation of PD-1/PD-L1 axis may contribute the MDS pathogenesis. Moreover, in patients treated with epigenetic therapy PD-L1 and PD-1 expression was upregulated indicating that induction of PD-1 and PD-1 ligands may be involved in hypomethylating agents (HMAs) resistance. PDCD1 polymorphisms are associated with susceptibility to several types of cancer.
Aims
We aim to characterize the PDCD1 expression and six PDCD1 polymorphisms in AML, MDS and s-AML patients samples as well as determine whether expression of PD-1 in those patients is driven by the genetic background.
Methods
PDCD1 mRNA expression was assessed in bone marrow mononuclear cells (BMMC) of 62 MDS, 54 AML and 8 s-AML patients samples using qRT-PCR method. Six SNP for PD-1 that demonstrate relevant associations with a higher risk of developing autoimmune diseases were assessed in AML, MDS and s-AML patients as well as 100 healthy volunteers (HVs): PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.6 (rs10204525), PD -1.7 (rs41386349), PD-1.9 (rs2227982). Moreover, immunohistochemical (IHC) stainings of 12 AML and 8 MDS bone marrow smears for PD-1 protein were performed.
Results
We observed significant decreased PDCD1 expression in AML group compared to HVs and MDS, (median: 0.0001 vs 0.0003, p<0.001 and 0.0001 vs 0.0003, p<0.001) but no differences in MDS and s-AML groups compared to HVs. IHC stainings showed PD-1 expression on blast cells in 6/12 AML and 6/8 MDS cases ranging from 1-92%. AML patients were stratified into three genetic groups according to prognosis: favorable risk, intermediate I risk and intermediate II / adverse risk and PDCD1 expression was compared between these groups. No significant differences were found between these groups. MDS patients were divided according to IPSS scoring systems into two groups: first with IPSS ranging from 0.0 to 0.5 and second with IPSS from 1 to 3. No significant difference were observed between these groups in case of PDCD1 expression (median: 0.0004 vs 0.0002, p=0.11). We observed significant differences in PDCD1 expression level regarding to PD-1.1.5 polymorphism. Moreover, analysis of a PD-1.1.3 polymorphism in HVs and MDS groups revealed that genotype GG was associated with nearly fivefold lower risk of disease (OR=4.93, p=0.009). We observed significant differences in OS in AML patients in case of presence of certain genotypes of PD-1.1.6. Genotype AA was significant associated with higher risk of shorter OS compared to the rest of the genotypes (58 vs 333 days, HR=35; p=0.0188).
Conclusion
We found significant differences in PDCD1 expression in AML and MDS patients that might indicate deregulation of a signal transduction through the PD-1/PD-L1 axis. By IHC stainings we were able to determine PD-1 expression on blast cells in 6/12 AML and 6/8 MDS bone marrow smears. Moreover, SNP analysis in AML patients revealed potential prognostic impact of PD-1.1.6 polymorphism.This work was supported by National Centre for Science Grant HARMONIA (UMO-2013/10/M/NZ5/00313).
Session topic: E-poster
Keyword(s): AML, MDS, Polymorphism
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