Myelodysplastic syndromes (MDS) and Myeloproliferative neoplasms (MPN) are myeloid malignancies with the potential for leukemic transformation. CALR and CD47 are biomarkers associated with phagocytosis, whose role in MDS and MPN has recently suggested CD47 as a strong anti-phagocytic signal responsible for cell survival. Other biomarkers have been associated with disease progression and/or treatment success but it is currently unknown how these biomarkers work together. The aim of this research was to investigate these biomarkers; GATA-1, BCL-2, PU.1 and JDP2 and compare their treatment response with CALR and CD47. MDS and MPN cell line models;SKM-1 and HEL-92, respectively, were treated with azacytidine or ruxolitinib, respectively. Western blot analysis was conducted in untreated and treated cells to quantify the expression of all proteins. Protein expression was standardised against GAPDH and compared using a t-test, p<0.05 was considered statistically significant. In the MDS cell line, upon azacytidine treatment, the expression of CALR and BCL-2 significantly (p<0.05) decreased (4.5-fold and 2-fold, respectively), PU.1 significantly (p<0.05) increased (1.8-fold) and CD47 and JDP2 increased. In the MPN cell line, the expression of all 5 proteins increased upon ruxolitinib treatment, where CALR and JDP2 expression significantly (p<0.05) increased (7.5-fold and 2-fold, respectively). This research supported CD47 as a strong anti-phagocytic signal. BCL-2 and CALR expression showed similar responses to treatment. CD47, PU.1 and JDP2 response to treatment was similar. Localisation and protein interaction studies are needed, along with human sample testing, to determine if these biomarkers could be useful as treatment response/prognostic markers or as therapeutic targets.
Subjects: MDS, MPN, protein expression, treatment response, prognostic scoring
Topics: protein expression, treatment response, disease progression
Dissertation written in collaboration with Kristian Boasman, Ciro Rinaldi, and Matthew Simmonds for submission to Blood Journal.
PLEASE NOTE: You must be a member of the University of Lincoln to be able to view this dissertation. Please log in here.