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• W2890876382 abstract "e18558 Background: PU.1 is a key transcription factor in haematopoiesis that plays important roles in various haematological malignancies. Previously, significant down-regulation of PU.1 has been reported in high risk myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) patients. Methods: To clarify PU.1 molecular function we investigated the gene expression of PU.1 and JDP2 (c-Jun dimerization protein-2), a member of the activating protein-1 family located downstream of PU.1, in bone marrow from 12 MDS patients stratified according to IPSS-R score (6-low, 3-intermediate, 3-high risk), 1 AML patient and 10 normal controls. Samples were enriched for the mononuclear fraction by Ficoll separation. Total RNA was extracted and analysed by Real Time PCR for PU.1 and JDP2 expression relative to the housekeeping gene GAPDHusing the 2-ΔΔCT method. Results: We revealed both PU.1 and JDP2 are down regulated in MDS. In addition, our data suggests that PU.1 and JDP2 expression inversely correlates with disease, with expression of these genes consistently reducing according to IPSS-R groups. Furthermore, a positive correlation of PU.1 and JDP2expression < R = O.9333, s = 0.0004 > , provides additional evidence that suppression of JDP2 by PU.1 could contribute to the pathogenesis of AML. Notably, PU.1 and JDP2 do not correlate to the same extent in normal HSCs, indicating that cofactors are required for PU.1 to exert its JDP2-regulating function and that such cofactors are not present under normal conditions. To confirm that JDP2 suppression is a direct result of reduced PU.1 we performed PU.1-knockdown in K562 cells stably expressing PU.1 short interfering RNAs versus control cells. These analyses reveal only a partial reduction in JDP2 expression when analysed by RT-PCR and Western blot, suggesting a more complex regulatory mechanism. Additionally, both PU.1 and JDP2 expression was recovered by treatment with azacitidine, which is routinely used to treat MDS, suggesting an involvement in treatment response. Conclusions: PU.1 and JDP2 expression correlates with patients prognosis highlighting a potential role as new diagnostic and prognostic markers in MDS." @default.
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• W2890876382 date "2017-05-20" @default.
• W2890876382 modified "2023-09-27" @default.
• W2890876382 title "Correlation of patient prognosis with PU.1 and JDP2 to provide potential novel prognostic/diagnostic markers in MDS." @default.
• W2890876382 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e18558" @default.
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