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  Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts

Blau, O., Baldus, C. D., Hofmann, W. K., Thiel, G., Nolte, F., Burmeister, T., et al. (2011). Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts. Blood, 118(20), 5583-92. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21948175 http://bloodjournal.hematologylibrary.org/content/118/20/5583.full.pdf.

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 Creators:
Blau, O., Author
Baldus, C. D., Author
Hofmann, W. K., Author
Thiel, G., Author
Nolte, F., Author
Burmeister, T., Author
Turkmen, S.1, Author           
Benlasfer, O., Author
Schumann, E., Author
Sindram, A., Author
Molkentin, M., Author
Mundlos, S.2, Author           
Keilholz, U., Author
Thiel, E., Author
Blau, I. W., Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: Abnormal Karyotype; Adult; Aged; Aged, 80 and over; Cell Transformation, Neoplastic/genetics; *Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 19; Female; Hematopoietic Stem Cells/pathology/physiology; Humans; Leukemia, Myeloid, Acute/*genetics/mortality/*pathology; Male; Mesenchymal Stromal Cells/*pathology/physiology; Middle Aged; Myelodysplastic Syndromes/*genetics/mortality/*pathology; Nuclear Proteins/genetics; Young Adult; fms-Like Tyrosine Kinase 3/genetics
 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.

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 Dates: 2011
 Publication Status: Issued
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Title: Blood
Source Genre: Journal
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Pages: - Volume / Issue: 118 (20) Sequence Number: - Start / End Page: 5583 - 92 Identifier: ISSN: 1528-0020 (Electronic) 0006-4971 (Linking)