title: Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors.
abstract: The bone marrow microenvironment may be permissive to the emergence and progression of acute myeloid leukemia (AML). Studying interactions between the microenvironment and leukemia cells should provide new insight for therapeutic advances. Mesenchymal stromal cells (MSCs) are central to the maintenance of the hematopoietic niche. Here we compared the functions and gene expression patterns of MSCs derived from bone marrow aspirates of healthy donors and patients with AML. MSCs expanded from AML patients had heterogeneous morphology and displayed a wide range of proliferation capacity compared to MSCs from healthy controls. The ability of AML-MSCs to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired while the expression of genes associated with maintaining hematopoietic quiescence appeared to be increased in AML-MSCs compared to healthy donors. These results highlight important potential differences in the biologic profile of MSCs from AML patients compared to healthy donors that may contribute to the emergence or progression of leukemia.
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Canada.
authors.forename: Priya
authors.initials: P
authors.lastname: Chandran
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Canada; Atomic Energy of Canada Limited, Chalk River, ON, Canada.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Le
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Canada.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine, Hematology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Sabloff
authors.affiliation: Centre for Biologics Evaluation, Health Canada, Ottawa, Canada.
authors.forename: Jelica
authors.initials: J
authors.lastname: Mehic
authors.affiliation: Centre for Biologics Evaluation, Health Canada, Ottawa, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosu-Myles
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Canada; Department of Medicine, Hematology, University of Ottawa, Ottawa, ON, Canada. Electronic address: daallan@ohri.ca.
authors.forename: David S
authors.initials: DS
authors.lastname: Allan
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018952:Antigens, CD34; D012333:RNA, Messenger
keywords: Acute myeloid leukemia; Hematopoiesis; Marrow microenvironment; Mesenchymal stromal cells