Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia.
OBJECTIVE
Bone marrow mesenchymal stroma cells (BMSC) are key components of the hematopoietic microenvironment. The question of whether BMSC from patients with hematological disorders have cytogenetic abnormalities is discussed controversially, some studies indicating that they are cytogenetically normal and others providing evidence of their aberrations.


METHODS
We performed standard and molecular cytogenetic analyses of both hematopoietic cells and BMSC from 31 patients with myelodysplastic syndrome (MDS, n = 18) and acute myeloid leukemia (AML, n = 13) and 7 healthy individuals. Mononuclear cells were isolated from fresh bone marrow aspirates at the time of initial diagnosis for cytogenetic analysis of hematopoietic cells (HC) and selection of BMSC.


RESULTS
Clonal cytogenetic aberrations were observed in HC from 8 (44%) MDS and 8 (61%) AML patients. Cytogenetic analyses of BMSC were successfully performed in 27 of the 31 cases. Structural chromosomal aberrations, including t(1;7), t(4;7), t(7;9), t(7;10), t(7;19), t(15;17), and others, were detectable in BMSC from 7 of 16 (44%) MDS and 6 of 11 (54%) AML patients. The breakpoints of chromosomes in BMSC were typical for leukemia aberrations. Two patients showed clonal chromosomal markers.


CONCLUSIONS
BMSC from MDS and AML patients show chromosomal abnormalities. Although the majority of cytogenetic aberrations in BMSC were not clonal and differed from chromosomal markers in HC from the same individual, detection of typical chromosomal changes in BMSC suggests enhanced genetic susceptibility of these cells in MDS/AML. This may indicate potential involvement of BMSC in the pathophysiology of MDS/AML.
Blau
Olga
O
Department of Hematology, Oncology and Transfusion Medicine, Charité-Campus Benjamin Franklin, University School of Medicine, Berlin, Germany. olga.marinets@charite.de
Hofmann
Wolf-Karsten
WK
Baldus
Claudia Dorothea
CD
Thiel
Gundula
G
Serbent
Verena
V
Schümann
Elke
E
Thiel
Eckhard
E
Blau
Igor Wolfgang
IW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000473:pathology*; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D011446:Prospective Studies; D017154:Stromal Cells / Q000473:pathology*