Alterations in the bone marrow microenvironment may elicit defective hematopoiesis: a comparison of aplastic anemia, chronic myeloid leukemia, and normal bone marrow

Abstract

Hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. The specific causes and mechanisms underlying dysregulated hematopoiesis are unknown. Here, BM biopsy specimens from patients with aplastic anemia (AA) and chronic myeloid leukemia (CML) and normal marrow were analyzed by semiquantitative immunohistochemistry to determine changes in the hematopoietic stem cell (HSC) compartment and BM microenvironment. HSC levels were lowest in AA and highest in CML. T and B lymphocytes were decreased in AA (p < 0.01) and CML (p < 0.01). Natural killer cells were observed in AA, but were absent in CML and healthy controls (p < 0.01). Macrophages and mast cells were absent in CML. There were significant differences between AA and CML stromal cell components. No nestin⁺ cells were observed in CML and the mean number of stromal cell-derived factor-1-positive cells was lowest in CML. Osteopontin⁺ cells were higher in AA than in CML (p < 0.01); osteonectin⁺ cells were higher in CML than in AA (p < 0.01). There was no significant difference in the expression of osteocalcin between AA and CML. The number of endothelial cells was highest in CML and lowest in AA (p < 0.01). Our findings suggest that changes in BM microenvironment components might be related to defective hematopoiesis leading to AA and/or CML.