Schaefer-Rego K E, Leibowitz D, Mears J G
Department of Medicine and Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York.
Oncogene. 1990 Nov;5(11):1669-73.
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.
慢性粒细胞白血病（CML）的特征是存在一种由22号染色体（ch）上的BCR基因部分与9号染色体上的ABL基因组成的新型融合基因。本研究旨在通过DNA酶I超敏反应确定调控DNA区域，以解决染色质改变是否导致ABL表达变化的问题。我们在K562细胞的异常BCR/ABL等位基因内鉴定出五个超敏（HS）位点，其模式与正常BCR不同。当细胞经历血红素诱导的分化时，超敏模式会发生改变。这些结果表明，正常BCR具有与活跃转录一致的染色质构型，而BCR/ABL融合基因的染色质则不同。这可能在CML的发病机制中起重要作用。
