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Altered Bone Marrow Niche: Predicting Outcomes in AML?

By: Melissa E. Fryman, MS
Posted: Friday, December 4, 2020

An altered balance between mesenchymal stem and progenitor cells seems to persist in the bone marrow microenvironment of patients with acute myeloid leukemia (AML), according to a study by Maher Hanoun, MD, and colleagues, of the University Hospital Essen, Germany. Such alterations within the bone marrow niche may inhibit osteogenesis and bone formation, with implications for clinical outcomes. The results of their study were published in the journal Blood Advances.

In this study, the researchers sampled peripheral blood and bone marrow from patients with AML at first diagnosis as well as that of patients with non-Hodgkin lymphoma without bone marrow involvement, and healthy donors. They quantified cell populations and reticular fibers, correlating immunohistochemical staining, and global gene-expression analyses to clinical features.

Compared with nonleukemic controls, the researchers found a significant increase in mesenchymal stem and progenitor cells as well as reticular fibers in samples from patients with AML. Moreover, these cell populations returned a distinct gene-expression profile, including higher expression of genes involved in proliferation and lower expression of genes involved in osteogenesis. When mesenchymal stem and progenitor cells were co-cultured with AML cells or healthy human peripheral blood mononuclear cells, osteoblast mineralization was impaired in the former—but not in the latter.

Lastly, the researchers found that for patients with AML who had lower levels of osteocalcin (≤ 11 ng/mL) at first diagnosis, the 1-year survival rate was 38.7%, compared with 66.8% in patients with higher osteocalcin levels.

“To what extent leukemia progression can be delayed by restoring osteoblast maturation is still pending,” the researchers concluded.

Disclosures: The authors reported no conflicts of interest.



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