By Melissa Badamo November 27, 2023
A recent study used comparative gene expression profiling to identify a subset of perturbed human bone marrow (BM) mesenchymal cells that can promote myelodysplastic syndromes (MDS), as well as niche changes that may delay disease progression.
Led by Youmna Kfoury, PhD, and published in Blood Advances, the goals of the study were to evaluate mesenchymal cell molecular features and to seek modifications that might affect MDS and offer additional therapeutic opportunities for patients.
Researchers collected frozen BM mononuclear cells of patients with MDS from multiple clinical centers, as well as BM filter bags from healthy donors. Researchers also conducted BM transplant experiments on mouse models, then performed gene expression analysis to compare the human population with the mouse subsets.
Perturbed BM mesenchymal cells were marked by the expression of nerve growth factor receptor (CD271), melanoma cell adhesion molecule (CD146), and vascular cell adhesion molecule (CD106), which resulted in hematopoietic dysplasia in the mesenchymal cells of mice.
The study also investigated the role of osteopontin (SPP1) in MDS progression by generating a chimeric model of an SPP1-KO mesenchymal environment. According to transcriptional analysis, SPP1 was the most overexpressed gene, and a lack of SPP1 in the mouse MDS microenvironment accelerated the progression of NUP98-HOXD13 (NHD13) dysplasia that resulted in a significant difference in survival. This acceleration was characterized by increased chimerism of NHD13 donor cells, higher mutant myeloid cell burden, and a more pronounced anemia compared with that in wild-type microenvironment controls.
Researchers noted that while SPP1 may constrain hematopoietic stem cell numbers, it appears to preserve their function.
“These results suggest that niche changes are not restricted to those that lead to disease progression, as has been suggested by prior reports,” researchers concluded. “Rather, we demonstrate that changes in SPP1 production may be protective and may serve to delay disease progression, ultimately protecting the host.”
Kfoury Y, Ji F, Jain E, et al. The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression. Blood Advances. 2023; doi.org/10.1182/bloodadvances.2022008268
Original Source: Molecular Perturbations in Bone Marrow Cells Could Promote Myelodysplastic Syndromes | Blood Cancers Today