Alterations within the osteo-hematopoietic niche in MDS and their therapeutic implications

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Anna Mies - , University Hospital Carl Gustav Carus Dresden, German Cancer Research Center (DKFZ), Department of internal Medicine I (Author)
  • Ekaterina Bulycheva - , University Hospital Carl Gustav Carus Dresden, Department of internal Medicine I (Author)
  • Inga Mandac Rogulj - , Merkur Clinical Hospital (Author)
  • Lorenz C. Hofbauer - , Center for Regenerative Therapies Dresden, Department of internal Medicine 3, University Hospital Carl Gustav Carus Dresden (Author)
  • Uwe Platzbecker - , University Hospital Carl Gustav Carus Dresden, German Cancer Research Center (DKFZ), Department of internal Medicine I (Author)

Abstract

Hematopoietic and mesenchymal stem and progenitor cells are organized in the osteo-hematopoietic niche, a complex microenvironment ensuring self-renewal and differentiation. Perturbations of the niche architecture, the mutual cellular interactions and signaling pathways disrupt tissue homeostasis resulting in cytopenia and malignant diseases such as myelodysplastic syndromes (MDS), supporting the concept of niche-induced oncogenesis. Analyzing the available treatment options for patients harboring MDS, it becomes evident that many of them specifically modify components of the stem cell niche. Hereby especially compounds inhibiting the TGF-β superfamily seem to represent a promising novel approach for patients with anemia as a result of ineffective erythropoiesis. Moreover, apart from affecting tumorigenesis, these drugs appear to influence bone structure and function as well as hematopoiesis in elderly MDS patients with a disturbed microarchitecture of the bone marrow. In the present review we will dissect the contribution of components of the stem cell niche for the pathogenesis of MDS and discuss current therapeutic strategies targeting components of the niche, focusing on the modulation of TGF-β signaling.

Details

Original languageEnglish
Pages (from-to)2323-2332
Number of pages10
JournalCurrent pharmaceutical design
Volume22
Issue number16
Publication statusPublished - 1 May 2016
Peer-reviewedYes

External IDs

PubMed 26916019
ORCID /0000-0002-8691-8423/work/164196675

Keywords

ASJC Scopus subject areas

Keywords

  • Bone marrow, HSPC, MDS, MSPC, Osteo-hematopoietic niche, Signaling, TGF-β