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Targeting the Microenvironment in MDS: The Final Frontier
- Source :
- Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 11 (2020)
- Publication Year :
- 2020
- Publisher :
- Frontiers Media SA, 2020.
-
Abstract
- Myelodysplastic syndromes (MDS) are a heterogeneous group of malignant disorders of hematopoietic stem and progenitor cells (HSPC), mainly characterized by ineffective hematopoiesis leading to peripheral cytopenias and progressive bone marrow failure. While clonal dominance is nearly universal at diagnosis, most genetic mutations identified in patients with MDS do not provide a conspicuous advantage to the malignant cells. In this context, malignant cells alter their adjacent bone marrow microenvironment (BME) and rely on cell extrinsic factors to maintain clonal dominance. The profoundly disturbed BME favors the myelodysplastic cells and, most importantly is detrimental to normal hematopoietic cells. Thus, the MDS microenvironment not only contributes to the observed cytopenias seen in these patients but could also negatively impact the engraftment of normal, allogeneic HSPCs in patients with MDS undergoing bone marrow transplant. Therefore, successful therapies in MDS should not only target the malignant cells but also reprogram their bone marrow microenvironment. Here, we will provide a synopsis of how drugs currently used or on the verge of being approved for the treatment of MDS may achieve this goal.
- Subjects :
- 0301 basic medicine
Mini Review
lenalidomide
03 medical and health sciences
0302 clinical medicine
hemic and lymphatic diseases
Medicine
Pharmacology (medical)
Progenitor cell
azacytidine
luspatercept
Lenalidomide
Pharmacology
Ineffective Hematopoiesis
CYP26 enzymes
business.industry
rigosertib
Myelodysplastic syndromes
lcsh:RM1-950
Rigosertib
Bone marrow failure
medicine.disease
microenvironment
all-trans retinoic acid
Haematopoiesis
lcsh:Therapeutics. Pharmacology
030104 developmental biology
medicine.anatomical_structure
myelodyslastic syndromes
030220 oncology & carcinogenesis
Cancer research
Bone marrow
business
medicine.drug
Subjects
Details
- ISSN :
- 16639812
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....ca6925e60d7666246799bbe94abb56e4