BCR/ABL P210 AND P190 CAUSE DISTINCT LEUKEMIA IN TRANSGENIC MICE
BCR/ABL P210 AND P190 CAUSE DISTINCT LEUKEMIA IN TRANSGENIC MICE
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DOI：
10.1182/blood.v86.12.4603.bloodjournal86124603
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发表时间：
1995-12-15
期刊：
影响因子：
20.3
通讯作者：
HEISTERKAMP, N
中科院分区：
文献类型：
--
作者：
VONCKEN, JW;KAARTINEN, V;HEISTERKAMP, N
编码BCR/ABL P210的DNA构建体已经通过显微注射单细胞受精卵被引入小鼠生殖系。转基因小鼠中BCR/ABL P210表达的动力学与转基因小鼠中BCR/ABL P190构建体的动力学非常相似。在胚胎发育早期和成年动物的造血组织中均可检测到mRNA转录物。外周血中BCR/ABL的表达先于显性疾病的发展。P210创始人和后代转基因动物生病时。在相对较长的潜伏期后发展为B、T淋巴或髓系来源的白血病。相比之下，P190转基因小鼠只发生B细胞来源的白血病，潜伏期相对较短。观察到的差异很可能是由于P190和P210癌蛋白的本质不同的性质，也可能涉及控制转基因表达的序列。转基因小鼠中BCR/ABL P210相关疾病的延迟进展与人类慢性髓性白血病慢性期的明显惰性一致。我们的结论是，在转基因模型中。BCR/ABL P210和BCR/ABL P190的相当表达导致临床上不同的病症。(C)1995年，美国血液学会。
DNA constructs encoding BCR/ABL P210 have been introduced into the mouse germ line using microinjection of one-cell fertilized eggs. Kinetics of BCR/ABL P210 expression in transgenic mice were very similar to those of BCR/ABL P190 constructs in transgenic mice. mRNA transcripts were detectable early in embryonic development and also in hematopoietic tissue of adult animals. Expression of BCR/ABL in peripheral blood preceded development of overt disease. P210 founder and progeny transgenic animals, when becoming ill. developed leukemia of B, T-lymphoid, or myeloid origin after a relatively long latency period. In contrast, P190-transgenic mice exclusively developed leukemia of B-cell origin, with a relatively short period of latency. The observed dissimilarities are most likely due to intrinsically different properties of the P190 and P210 oncoproteins and may also involve sequences that control transgene expression. The delayed progression of BCR/ABL P210-associated disease in the transgenic mice is consistent with the apparent indolence of human chronic myeloid leukemia during the chronic phase. We conclude that, in transgenic models. comparable expression of BCR/ABL P210 and BCR/ABL P190 results in clinically distinct conditions. (C) 1995 by The American Society of Hematology.