Cytogenetic and Molecular Genetic Aberrations in Bone Marrow Mesenchymal Stroma Cells from Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia
| Autor: | Olga Blau, Elke Schuemann, Annette Sindram, Verena Nowak, Korinna Kuehne, Igor Wolfgang Blau, Eckhard Thiel, Wolf-Karsten Hofmann, Gundula Thiel, Claudia D. Baldus |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Blood. 110:985-985 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Introduction : The biology of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is heterogeneous. Ineffective hematopoiesis results from complex interactions between hematopoietic cells (HC) and the hematopoietic microenvironment. 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. Methods: We performed standard cytogenetic analyses (G-banding), FISH, M-FISH, and FLT3 mutation examinations of both HC and BMSC from 56 patients (30 MDS and 26 AML) and 9 healthy individuals. For BMSC selection, mononuclear cells were isolated from fresh bone marrow aspirates at the time of initial diagnosis and were further expanded in cell culture. Results: Clonal cytogenetic aberrations were observed in HC from 14 (46%) MDS and 14 (53%) AML patients. Cytogenetic analyses of BMSC were successfully performed in 50 of the 56 cases. Structural chromosomal aberrations, including t(1;7); t(1;3); t(1;10); t(4;7); t(7;9); t(7;19); i(1q); inv(X); del(1q); del(2q); del(3p); del(4p); del(11q); del(13q); del(17p), and others were detectable in BMSC from 42% of patients. The breakpoints of chromosomes in BMSC were typical for leukemia aberrations. Six patients showed clonal chromosomal markers: t(1;7), t(1;10), t(7;9), inv(X), del(17p), and monosomy 4. Interestingly, cytogenetic markers in BMSC differed to the aberrations in HC from the same individual. No deletions or monosomy of chromosomes 5 or 7 in BMSC (FISH, 500 cells) were found in BMSC, even in those patients, who showed these aberrations in HC. M-FISH confirmed chromosomal aberrations in BMSC. We have found cytogenetic abnormalities in BMSC from patients presenting with cytogenetic alterations in their HC as well as from those with normal karyotype. We did not find structural chromosomal alterations in BMSC cultures of healthy bone marrow donors. Fourteen percent of AML patients showed FLT3 mutations in HC, but no FLT3 mutations were found in BMSC. Conclusion: We showed that BMSC from AML and especially from MDS patients are characterized by genetic instability. The breakpoints of chromosomes in BMSC were typical for leukemia aberrations. The fact that BMSC showed typical chromosomal changes may suggest enhanced genetic susceptibility and potential involvement in the pathophysiology of MDS. Characterization of BMSC may help us to better understand the biology of this disease. |
| Databáze: | OpenAIRE |
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