title: Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration.
abstract: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play a fundamental role in the BM microenvironment (BME) and abnormalities of these cells may contribute to acute myeloid leukemia (AML) pathogenesis. The aim of the study was to characterize the cytokine and gene expression profile, immunophenotype and cytogenetics of BM-MSCs from AML patients compared to normal BM-MSCs from healthy donors. AML BM-MSCs showed decreased monocyte chemoattractant protein-1 levels compared to normal BM-MSCs. AML BM-MSCs expressed similar β1 integrin, CD44, CD73, CD90 and E-cadherin compared to normal BM-MSCs. Cytogenetic analysis revealed chromosomal aberrations in AML BM-MSCs, some overlapping with and others distinct from their corresponding AML blasts. No significant difference in gene expression was detected between AML BM-MSCs compared to normal BM-MSCs; however, comparing the differences between AML and MSCs from AML patients with the differences between normal hematopoietic cells and normal MSCs by Ingenuity pathway analysis showed key distinctions of the AML setting: (1) upstream gene regulation by transforming growth factor beta 1, tumor necrosis factor, tissue transglutaminase 2, CCAAT/enhancer binding protein alpha and SWItch/Sucrose NonFermentable related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; (2) integrin and interleukin 8 signaling as overrepresented canonical pathways; and (3) upregulation of transcription factors FBJ murine osteosarcoma viral oncogene homolog and v-myb avian myeloblastosis viral oncogene homolog. Thus, phenotypic abnormalities of AML BM-MSCs highlight a dysfunctional BME that may impact AML survival and proliferation.
authors: 1] Division of Hematology, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA [2] Division of Gerontology & Geriatric Medicine, University of Washington, Seattle, WA, USA.
authors: J C
authors: JC
authors: Huang
authors: Section of Hematology & Oncology, West Virginia University School of Medicine, Morgantown, WV, USA.
authors: S K
authors: SK
authors: Basu
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: X
authors: X
authors: Zhao
authors: Division of Hematology, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA.
authors: S
authors: S
authors: Chien
authors: 1] Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Department of Pathology and Laboratory Medicine, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA.
authors: M
authors: M
authors: Fang
authors: 1] Division of Hematology, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA [2] Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: V G
authors: VG
authors: Oehler
authors: 1] Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors: F R
authors: FR
authors: Appelbaum
authors: 1] Division of Hematology, Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA [2] Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: P S
authors: PS
authors: Becker
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2