Genomics

Dataset Information

36

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


ABSTRACT: 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. Overall design: Analysis of gene expression in fibroblast and macrophage populations isolated from primary long-term bone marrow cultures (LTBMC). Adherent layers of LTBMCs were trypsinized, fibroblasts and macrophages were purified using anti-Fibroblast or CD14 MicroBeads (Miltenyi Biotec, Begisch-Gladbach, Germany), and total RNA was extracted by using the RNeasy kit from Qiagen (Hilden, Germany), as specified by the manufacturer. Global gene expression was analyzed in 4 samples each of fibroblasts and macrophages from AML patients and control subjects.

INSTRUMENT(S): [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array

SUBMITTER: Ludger Klein-Hitpass  

PROVIDER: GSE26294 | GEO | 2015-12-21

SECONDARY ACCESSION(S): PRJNA135055

REPOSITORIES: GEO

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Publications

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

Li Yu Y   Dürig Jan J   Göbel Maria M   Hanoun Maher M   Klein-Hitpaß Ludger L   Dührsen Ulrich U  

International journal of hematology 20150628 3


In bone marrow malignancies, little is known about the fate of stromal cells after replacement of normal cells by neoplastic hematopoietic ones. In this study, fibroblasts from patients with acute myeloid leukemia or myelodysplastic syndromes exhibited a significantly lower ability to support hematopoiesis originating from co-cultured allogeneic CD34-positive cells than did fibroblasts from healthy marrow. Conversely, macrophages from acute myeloid leukemia marrow significantly enhanced the prod  ...[more]