Contributions
Abstract: PB2087
Type: Publication Only
Background
Aldehyde dehydrogenases (ALDH) are critical to the protection against toxic aldehydes and have been associated with multiple diseases, namely with cancer. Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are two myeloid neoplasias with a complex multistep development involving abnormal differentiation, cellular proliferation, and apoptosis. Since ALDHs are involved in some of these biological processes, the deregulation of these enzymes may influence MDS and AML development.
Aims
This study aimed to evaluate the gene expression levels of ALDHs isoenzymes in patients with MDS and AML in order to verify their potential as a biomarker for the diagnosis and/or prognosis of these diseases.
Methods
To this end, we analyzed the gene expression levels of ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1, ALDH7A1, ALDH16A1, and ALDH18A1. The ALDH expression levels were analyzed using RT-PCR and the differentially expressed genes were quantified by qPCR. This study enrolled 34 MDS patients [median age of 72 years (ranging from 49 to 89 years) and 59% males], 20 AML [median age of 56 years (ranging from 26 to 92 years) and 45% males], and 34 healthy controls [median age of 70 years (ranging from 32 to 88 years) and 59% males]. According to the 2016 WHO classification, MDS group included: 4 MDS with single lineage dysplasia (MDS-SLD), 15 MDS with multilineage dysplasia (MDS-MD), 7 myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 4 MDS with excess blasts (MDS-EB), 3 MDS with ring sideroblasts (MDS-RS), and 1 MDS associated with isolated del(5q). According to WPSS, 5 MDS patients have very low risk, 9 low risk, 6 intermediate risk, 2 high risk, 1 very high risk (4.4%), and 11 patients were unclassified. The AML group included 7 AML with minimal differentiation (AML-MD), 5 acute myelomonocytic leukemia, 4 acute promyelocytic leukemia with PML-RARA, and 4 AML with myelodysplasia-related changes (AML-MRD). The statistical analysis was carried out by uni- and multivariate tests. A value of p<0.05 was considered significant.
Results
The results indicate that ALDH3A2, ALDH3B1, ALDH4A1, and ALDH18A1 had a differential expression among the study groups and were posteriorly quantified by real-time PCR. MDS and AML patients showed higher median expression levels of ALDH3A2 [MDS: 1.93 interquartile range (IR) 1.28; p<0.001; AML: 1.51 IR 0.99; p=0.008)] and ALDH4A1 (MDS: 0.18 IR 0.47; p=0.011; AML: 0.16 IR 0.78; p=0.012) in comparison with controls (ALDH3A2: 0.4624 IR 1.53 ALDH4A1: 0.0388 IR 0.12). The expression of ALDH3B1 was higher in MDS patients (1.64 IR 1.39) than in AML patients (0.45 IR 0.47; p<0.001) and controls (0.35 IR 0.51; p<0.001). Moreover, this isoenzyme was significantly higher in MDS-SLD and in very low-risk patients (WPSS) comparatively with the others subgroups. Additionally, patients with MDS and AML with myelodysplasia-related changes (AML-MRC) did not express ALDH18A1. ROC curve analysis showed that ALDH3A2 (p=0.001), ALDH3B1 (p<0.001), and ALDH4A1 (p=0.012) were able to discriminate MDS patients from controls. Moreover, ALDH3A2 was the only isoform with diagnostic value for AML patients.
Conclusion
ALDH isoforms have differential expression patterns in MDS and AML patients when compared to controls and with each other, and can be good diagnostic biomarkers of these diseases. However, further studies are needed to prove the potential of these enzymes as diagnostic/prognostic biomarkers.
This work was supported by CIMAGO and by the FCT through the fellowship SFRH/BD/51994/2012.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): MDS/AML, Myeloid malignancies, Aldehyde dehydrogenase, Diagnosis
Abstract: PB2087
Type: Publication Only
Background
Aldehyde dehydrogenases (ALDH) are critical to the protection against toxic aldehydes and have been associated with multiple diseases, namely with cancer. Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are two myeloid neoplasias with a complex multistep development involving abnormal differentiation, cellular proliferation, and apoptosis. Since ALDHs are involved in some of these biological processes, the deregulation of these enzymes may influence MDS and AML development.
Aims
This study aimed to evaluate the gene expression levels of ALDHs isoenzymes in patients with MDS and AML in order to verify their potential as a biomarker for the diagnosis and/or prognosis of these diseases.
Methods
To this end, we analyzed the gene expression levels of ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1, ALDH7A1, ALDH16A1, and ALDH18A1. The ALDH expression levels were analyzed using RT-PCR and the differentially expressed genes were quantified by qPCR. This study enrolled 34 MDS patients [median age of 72 years (ranging from 49 to 89 years) and 59% males], 20 AML [median age of 56 years (ranging from 26 to 92 years) and 45% males], and 34 healthy controls [median age of 70 years (ranging from 32 to 88 years) and 59% males]. According to the 2016 WHO classification, MDS group included: 4 MDS with single lineage dysplasia (MDS-SLD), 15 MDS with multilineage dysplasia (MDS-MD), 7 myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 4 MDS with excess blasts (MDS-EB), 3 MDS with ring sideroblasts (MDS-RS), and 1 MDS associated with isolated del(5q). According to WPSS, 5 MDS patients have very low risk, 9 low risk, 6 intermediate risk, 2 high risk, 1 very high risk (4.4%), and 11 patients were unclassified. The AML group included 7 AML with minimal differentiation (AML-MD), 5 acute myelomonocytic leukemia, 4 acute promyelocytic leukemia with PML-RARA, and 4 AML with myelodysplasia-related changes (AML-MRD). The statistical analysis was carried out by uni- and multivariate tests. A value of p<0.05 was considered significant.
Results
The results indicate that ALDH3A2, ALDH3B1, ALDH4A1, and ALDH18A1 had a differential expression among the study groups and were posteriorly quantified by real-time PCR. MDS and AML patients showed higher median expression levels of ALDH3A2 [MDS: 1.93 interquartile range (IR) 1.28; p<0.001; AML: 1.51 IR 0.99; p=0.008)] and ALDH4A1 (MDS: 0.18 IR 0.47; p=0.011; AML: 0.16 IR 0.78; p=0.012) in comparison with controls (ALDH3A2: 0.4624 IR 1.53 ALDH4A1: 0.0388 IR 0.12). The expression of ALDH3B1 was higher in MDS patients (1.64 IR 1.39) than in AML patients (0.45 IR 0.47; p<0.001) and controls (0.35 IR 0.51; p<0.001). Moreover, this isoenzyme was significantly higher in MDS-SLD and in very low-risk patients (WPSS) comparatively with the others subgroups. Additionally, patients with MDS and AML with myelodysplasia-related changes (AML-MRC) did not express ALDH18A1. ROC curve analysis showed that ALDH3A2 (p=0.001), ALDH3B1 (p<0.001), and ALDH4A1 (p=0.012) were able to discriminate MDS patients from controls. Moreover, ALDH3A2 was the only isoform with diagnostic value for AML patients.
Conclusion
ALDH isoforms have differential expression patterns in MDS and AML patients when compared to controls and with each other, and can be good diagnostic biomarkers of these diseases. However, further studies are needed to prove the potential of these enzymes as diagnostic/prognostic biomarkers.
This work was supported by CIMAGO and by the FCT through the fellowship SFRH/BD/51994/2012.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): MDS/AML, Myeloid malignancies, Aldehyde dehydrogenase, Diagnosis