title: Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts.
abstract: Mesenchymal stromal cells (MSCs) are an essential cell type of the hematopoietic microenvironment. Concerns have been raised about the possibility that MSCs undergo malignant transformation. Several studies, including one from our own group, have shown the presence of cytogenetic abnormalities in MSCs from leukemia patients. The aim of the present study was to compare genetic aberrations in hematopoietic cells (HCs) and MSCs of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients. Cytogenetic aberrations were detected in HCs from 25 of 51 AML patients (49%) and 16 of 43 MDS patients (37%). Mutations of the FLT3 and NPM1 genes were detected in leukemic blasts in 12 (23%) and 8 (16%) AML patients, respectively. Chromosomal aberrations in MSCs were detected in 15 of 94 MDS/AML patients (16%). No chromosomal abnormalities were identified in MSCs of 36 healthy subjects. We demonstrate herein that MSCs have distinct genetic abnormalities compared with leukemic blasts. We also analyzed the main characteristics of patients with MSCs carrying chromosomal aberrations. In view of these data, the genetic alterations in MSCs may constitute a particular mechanism of leukemogenesis.
authors.affiliation: Department of Hematology and Oncology, Charité University School of Medicine, Hindenburgdamm 30, Berlin, Germany. olga.blau@charite.de
authors.forename: Olga
authors.initials: O
authors.lastname: Blau
authors.forename: Claudia Dorothea
authors.initials: CD
authors.lastname: Baldus
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Gundula
authors.initials: G
authors.lastname: Thiel
authors.forename: Florian
authors.initials: F
authors.lastname: Nolte
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Seval
authors.initials: S
authors.lastname: Türkmen
authors.forename: Ouidad
authors.initials: O
authors.lastname: Benlasfer
authors.forename: Elke
authors.initials: E
authors.lastname: Schümann
authors.forename: Annette
authors.initials: A
authors.lastname: Sindram
authors.forename: Mara
authors.initials: M
authors.lastname: Molkentin
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Igor Wolfgang
authors.initials: IW
authors.lastname: Blau
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology* / Q000502:physiology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3