Chromatin alterations surrounding the BCR/ABL fusion gene in K562 cells.
Chronic myelogenous leukemia (CML) is characterized by the presence of a novel fusion gene comprised of portions of the BCR gene from chromosome (ch) 22 and the ABL gene from ch 9. The present study was designed to identify regulatory DNA regions as determined by DNAase I hypersensitivity to address the question of whether altered chromatin contributes to changes in ABL expression. We identify five hypersensitive (HS) sites within the abnormal BCR/ABL allele in K562 cells in a pattern different from the normal BCR. The pattern of hypersensitivity is modified when the cells undergo hemin induced differentiation. These results indicate that the normal BCR has a chromatin configuration consistent with active transcription and that the BCR/ABL fusion gene chromatin is different. This may be important in the pathogenesis of CML.
Schaefer-Rego
K E
KE
Department of Medicine and Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York.
Leibowitz
D
D
Mears
J G
JG
D002843:Chromatin / Q000648:ultrastructure*; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics*; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005784:Gene Amplification; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D010677:Philadelphia Chromosome; D015183:Restriction Mapping; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D002843:Chromatin; D015342:DNA Probes; D004273:DNA, Neoplasm; D006427:Hemin; D016044:Fusion Proteins, bcr-abl; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; C029312:GGTACC-specific type II deoxyribonucleases; D015689:Oncogene Protein p21(ras)