Cytogenetic characterization of a BCR-ABL transduced mouse cell line.
Most patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL) show evidence of secondary chromosome aberrations that may influence the course of disease and response to treatment. To better understand how these secondary chromosomal aberrations occur and to investigate whether the p185/p190 BCR-ABL fusion protein may directly induce an increased chromosomal instability and subsequently the appearance of clonal chromosome aberrations, three BRC-ABL (p185/ p190)-transduced mouse pre-B cell lines were analyzed by spectral karyotyping and fluorescence in situ hybridization. The human wild-type BCR-ABL gene was expressed at a level comparable with that in human Ph-positive leukemias at diagnosis. All BCR-ABL-transduced cell lines acquired similar clonal chromosomal aberrations. Trisomy 5 was always present, followed by loss of the Y chromosome, trisomy of chromosomes 12 and 18, and an unbalanced translocation between chromosomes X and 12. Thus, ectopic p185/p190 BCR-ABL expression, such as p210 BCR-ABL, PML-RARA, or C-MYC transduction, may induce an increased chromosomal instability leading to clonal karyotypic evolution, which may mimic secondary chromosome aberrations in human Ph-positive ALL.
Rudolph
Cornelia
C
Institute of Cell and Molecular Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Hegazy
Ahmed N
AN
von Neuhoff
Nils
N
Steinemann
Doris
D
Schröck
Evelin
E
Stripecke
Renata
R
Klein
Christoph
C
Schlegelberger
Brigitte
B
D000818:Animals; D002461:Cell Line, Transformed; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010677:Philadelphia Chromosome; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032681:Spectral Karyotyping; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016044:Fusion Proteins, bcr-abl