Using PU.1 and Jun dimerization protein 2 transcription factor expression in myelodysplastic syndromes to predict treatment response and leukaemia transformation
Myelodysplastic syndromes (MDS) are malignant disorders of myeloid progenitors, characterised by bone marrow failure, peripheral cytopenias and progression to acute myeloid leukaemia (AML) . Currently, the DNA methyltransferase 1 (DNMT1) depleting drugs 5-azacytidine and decitabine are the only drugs approved in the USA to treat all subtypes of MDS. Unfortunately, only 40–50% of patients achieve some response with these drugs, and these are not typically durable beyond some months or years. Whilst it is known, these drugs repressive epigenetic modifications of chromatin caused by DNA methylation, to presumably reactivate tumour suppressor genes , the specific gene/s targeted are unknown. PU.1 is a master transcription factor driving granulocyte and monocyte lineage fates, and partial loss-of-function of PU.1 has been shown to induce AML onset in mice and humans [2, 3]. The most frequent acquired mutation in de novo AMLs, is in nucleophosmin (NPM1). The NPM1 protein...
The authors thank Rachael Simpson for her contribution towards some of the experimental assays.
This study was funded by Celgene Pharma.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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