Functional abnormalities and changes in gene expression in fibroblasts and macrophages from the bone marrow of patients with acute myeloid leukemia

In leukemias and other malignancies of the bone marrow, little is known about the fate of fibroblasts and resident macrophages after normal hematopoietic cells are replaced by neoplastic cells. In the present investigation we used two-stage long-term bone marrow cultures to detect functional stromal cell abnormalities in acute myeloid leukemia, myelodysplastic syndromes and multiple myeloma. While fibroblasts from multiple myeloma and macrophages from multiple myeloma and myelodysplastic syndromes were functionally indistinguishable from the respective cell types from normal bone marrow, fibroblasts from patients with acute myeloid leukemia or myelodysplastic syndromes possessed a significantly lower ability to support hematopoiesis originating from co-cultured normal CD34-positive cells than fibroblasts from healthy marrow. Conversely, macrophages from acute myeloid leukemia marrow significantly enhanced the production of blood cells compared with control macrophages. Aberrant function in fibroblasts and macrophages was associated with consistent changes in the expression of genes whose products are involved in hematopoietic stem cell control, such as cytokines and regulators of the Wnt and Notch signalling pathways.

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Li Y, Dürig J, Göbel M, Hanoun M, Klein-Hitpaß L, Dührsen U