Please use this identifier to cite or link to this item: https://hdl.handle.net/1/1275
Title: The oral iron chelator deferasirox inhibits NF-kappaB mediated gene expression without impacting on proximal activation: implications for myelodysplasia and aplastic anaemia
Authors: Forsyth, Cecily J ;Banerjee, A.;Mifsud, N. A.;Bird, R.;Szer, J.;Tam, C.;Kellner, S.;Grigg, A.;Motum, P.;Bentley, M.;Opat, S.;Grigoriadis, G.
Issue Date: Feb-2015
Source: Volume 168, Issue 4, pp. 576-582
Journal title: British Journal of Haematology
Abstract: The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-kappaB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-kappaB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies.
URI: https://elibrary.cclhd.health.nsw.gov.au/cclhdjspui/handle/1/1275
DOI: 10.1111/bjh.13151
Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/25271366
ISSN: 0007-1048
Publicaton type: Journal Article
Keywords: Hematology
Haematology
Anaemia
Anemia
Appears in Collections:Haematology

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