Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitro Article Swipe
Zhijian Liu
,
Emöke Deschmann
,
Haley E. Ramsey
,
Henry A. Feldman
,
Bethan Psaila
,
Nichola Cooper
,
Evangelia Vlachodimitropoulou
,
John B. Porter
,
James B. Bussel
,
Michael Georgieff
,
Martha Sola‐Visner
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2021004207
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2021004207
Eltrombopag (ELT) is a thrombopoietic agent approved for immune thrombocytopenia and also a potent iron chelator. Here we found that ELT exhibited dose-dependent opposing effects on in vitro megakaryopoiesis: low concentrations (≤6 µM, ELT6) stimulated megakaryopoiesis, but high concentrations (30 µM, ELT30) suppressed megakaryocyte (MK) differentiation and proliferation. The suppressive effects of ELT30 were reproduced by other iron chelators, supporting iron chelation as a likely mechanism. During MK differentiation, committed MK progenitors (CD34+/CD41+ and CD34−/CD41+ cells) were significantly more sensitive than undifferentiated progenitors (CD34+/CD41− cells) to the suppressive effects of ELT30, which resulted from both decreased proliferation and increased apoptosis. The antiproliferative effects of ELT30 were reversed by increased iron in the culture, as were the proapoptotic effects when exposure to ELT30 was short. Because committed MK progenitors exhibited the highest proliferative rate and the highest sensitivity to iron chelation, we tested whether their iron status influenced their response to ELT during rapid cell expansion. In these studies, iron deficiency reduced the proliferation of CD41+ cells in response to all ELT concentrations. Severe iron deficiency also reduced the number of MKs generated in response to high thrombopoietin concentrations by ∼50%, compared with iron-replete cultures. Our findings support the hypothesis that although iron deficiency can stimulate certain cells and steps in megakaryopoiesis, it can also limit the proliferation of committed MK progenitors, with severity of iron deficiency and degree of thrombopoietic stimulation influencing the ultimate output. Further studies are needed to clarify how megakaryopoiesis, iron deficiency, and ELT stimulation are clinically interrelated.
Related Topics
Concepts
Thrombopoietin
Progenitor cell
Megakaryocyte
Stimulation
Eltrombopag
Iron deficiency
Cell biology
Chemistry
CD34
Haematopoiesis
Immunology
Cord blood
Internal medicine
Endocrinology
Andrology
Biology
Stem cell
Immune thrombocytopenia
Medicine
Platelet
Anemia
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1182/bloodadvances.2021004207
- https://ashpublications.org/bloodadvances/article-pdf/6/1/13/1856171/advancesadv2021004207.pdf
- OA Status
- gold
- Cited By
- 3
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3206987004
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3206987004Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1182/bloodadvances.2021004207Digital Object Identifier
- Title
-
Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitroWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-10-20Full publication date if available
- Authors
-
Zhijian Liu, Emöke Deschmann, Haley E. Ramsey, Henry A. Feldman, Bethan Psaila, Nichola Cooper, Evangelia Vlachodimitropoulou, John B. Porter, James B. Bussel, Michael Georgieff, Martha Sola‐VisnerList of authors in order
- Landing page
-
https://doi.org/10.1182/bloodadvances.2021004207Publisher landing page
- PDF URL
-
https://ashpublications.org/bloodadvances/article-pdf/6/1/13/1856171/advancesadv2021004207.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://ashpublications.org/bloodadvances/article-pdf/6/1/13/1856171/advancesadv2021004207.pdfDirect OA link when available
- Concepts
-
Thrombopoietin, Progenitor cell, Megakaryocyte, Stimulation, Eltrombopag, Iron deficiency, Cell biology, Chemistry, CD34, Haematopoiesis, Immunology, Cord blood, Internal medicine, Endocrinology, Andrology, Biology, Stem cell, Immune thrombocytopenia, Medicine, Platelet, AnemiaTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2022: 2Per-year citation counts (last 5 years)
- References (count)
-
40Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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