Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia.
Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature lymphocytes. Even though childhood ALL can be cured in a large number of patients, around 20% of the patients suffer a relapse after chemotherapy. The origin of the relapse is unclear at the present time. Given the high plasticity of cells, we searched for leukemia-associated genetic aberrations and immunoglobulin (IG) gene rearrangements in mesenchymal stem cells (MSC) from childhood B-cell precursor ALL patients. MSC from all ten ALL patients analyzed presented the chromosomal translocations that had been detected in leukemia cells (TEL-AML1, E2A-PBX1, or MLL rearrangement). The proportions of translocation-positive MSC varied between 10% and 54% depending on the patients and the time point of analysis. Leukemia-specific IG gene rearrangements were detected in the MSC from three ALL patients. The detection of leukemia-associated genetic aberrations in MSC indicates a clonal relationship between MSC and leukemia cells and suggests their involvement in the pathogenesis and/or pathophysiology of childhood ALL.
Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. Shabnam.shalapour@charite.de
Shabnam
S
Shalapour
Cornelia
C
Eckert
Karl
K
Seeger
Madlen
M
Pfau
Javier
J
Prada
Günter
G
Henze
Thomas
T
Blankenstein
Thomas
T
Kammertoens
D001483:Base Sequence; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein