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ALDHs as potential biomarkers in myeloid neoplasms – Preliminary study
B. Macedo1,, , J. Jorge2,3, R. Alves2,3, A.C. Gonçalves2,3,4, A.B. Sarmento-Ribeiro2,3,4,5
1 Department of Chemistry, University of Aveiro, Portugal
2 Laboratory of Oncobiology and Hematology, University Clinic of Hematology and Applied Molecular Biology, Faculty of Medicine, University of Coimbra, Portugal
3 Center for Neuroscience and Cell Biology, IBILI, University of Coimbra, Portugal
4 CIMAGO – Center of Investigation on Environment Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal
5 Clinical Hematology Service, University Hospital of Coimbra, Portugal

Aim: The aim of the study is to evaluate the expression of aldehyde dehydrogenase (ALDH) in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) to verify their potential as a marker for the diagnosis and/or prognosis of these diseases.

Introduction: ALDH superfamily is a group of 19 enzymes critical to the protection against toxic aldehydes, and have been associated with multiple diseases, namely in cancer. MDS are characterized by ineffective hematopoiesis associated with progressive peripheral blood cytopenias, and a predisposition toward leukemic transformation. MDS pathophysiology is a complex multistep process that involves genetic and epigenetic abnormalities in genes associated with 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.

Methods: To this end, we analyzed the expression levels of 8 ALDH isoforms, ALDH1A1, ALDH1A2 ALDH1B1, ALDH1L1, ALDH1L2, ALDH3A2, ALDH4A1, and ALDH16A1, in 31 patients (16 MDS and 15 LMA) and 19 healthy controls. ALDH expression levels were analyzed using RT-PCR and differentially expressed genes were quantified by qPCR. The statistical analysis was carried out by variance analysis and χ2 test. Survival were analyzed by Kaplan Meier curves (p<0.05).

Results: Preliminary results indicate that all MDS patients express ALDH16A1 isoform whereas only 67% of controls (p<0.05) show expression of this isoform. Moreover, AML patients have lower ALDH1A2 expression levels than MDS and controls and only 20% of AML patients express this isoform (MDS=54% and controls=55%). The ALDH1L2 is only expressed in chronic myelomonocytic leukemia subtype of MDS. Furthermore, the expression of ALDH isoforms does not appear to influence patient overall survival.

Conclusion: According to these results, ALDH isoforms have differential expression patterns in MDS and AML patients when compared with controls and each other. Further studies are needed to prove their potential as a diagnostic/prognostic biomarkers.

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