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论文题目: Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin
英文论文题目: Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin
第一作者: Man, N; Sun, XJ; Tan, YR; Garcia-Cao, M; Liu, F; Cheng, GY; Hatlen, M; Xu, HM; Shah, R; Chastain, N; Liu, N; Huang, G; Zhou, Y; Sheng, MY; Song, JH; Yang, FC; Benezra, R; Nimer, SD; Wang, L
英文第一作者: Man, N; Sun, XJ; Tan, YR; Garcia-Cao, M; Liu, F; Cheng, GY; Hatlen, M; Xu, HM; Shah, R; Chastain, N; Liu, N; Huang, G; Zhou, Y; Sheng, MY; Song, JH; Yang, FC; Benezra, R; Nimer, SD; Wang, L
联系作者: Wang, L (reprint author), Shanghai Jiao Tong Univ, Inst Hlth Sci, Shanghai Inst Biol Sci, Chinese Acad Sci,Sch Med, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Wang, L (reprint author), Shanghai Jiao Tong Univ, Inst Hlth Sci, Shanghai Inst Biol Sci, Chinese Acad Sci,Sch Med, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 127
期: 19
页码: 2322-2326
摘要: Inhibitor of DNA binding 1 (Id1) functions as an E protein inhibitor, and overexpression of Id1 is seen in acute myeloid leukemia (AML) patients. To define the effects of Id1 on leukemogenesis, we expressed MLL-AF9 in fetal liver (FL) cells or bone marrow (BM) cells isolated from wild-type, Id1(-/-), p21(-/-), or Id1(-/-) p21(-/-) mice, and transplanted them into syngeneic recipient mice. We found that although mice receiving MLL-AF9-transduced FL or BM cells develop AML, loss of Id1 significantly prolonged the median survival of mice receiving FL cells but accelerated leukemogenesis in recipients of BM cells. Deletion of Cdkn1a (p21), an Id1 target gene, can rescue the effect of Id1 loss in both models, suggesting that Cdkn1a is a critical target of Id1 in leukemogenesis. It has been suggested that the FL transplant model mimics human fetal-origin (infant) MLL fusion protein (FP)driven leukemia, whereas the BM transplantation model resembles postnatal MLL leukemia; in fact, the analysis of clinical samples from patients with MLL-FP 1 leukemia showed that Id1 expression is elevated in the former and reduced in the latter type of MLL-FP 1 AML. Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9-driven leukemia.
英文摘要: Inhibitor of DNA binding 1 (Id1) functions as an E protein inhibitor, and overexpression of Id1 is seen in acute myeloid leukemia (AML) patients. To define the effects of Id1 on leukemogenesis, we expressed MLL-AF9 in fetal liver (FL) cells or bone marrow (BM) cells isolated from wild-type, Id1(-/-), p21(-/-), or Id1(-/-) p21(-/-) mice, and transplanted them into syngeneic recipient mice. We found that although mice receiving MLL-AF9-transduced FL or BM cells develop AML, loss of Id1 significantly prolonged the median survival of mice receiving FL cells but accelerated leukemogenesis in recipients of BM cells. Deletion of Cdkn1a (p21), an Id1 target gene, can rescue the effect of Id1 loss in both models, suggesting that Cdkn1a is a critical target of Id1 in leukemogenesis. It has been suggested that the FL transplant model mimics human fetal-origin (infant) MLL fusion protein (FP)driven leukemia, whereas the BM transplantation model resembles postnatal MLL leukemia; in fact, the analysis of clinical samples from patients with MLL-FP 1 leukemia showed that Id1 expression is elevated in the former and reduced in the latter type of MLL-FP 1 AML. Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9-driven leukemia.
刊物名称: BLOOD
英文刊物名称: BLOOD
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学科: Hematology
英文学科: Hematology
影响因子: 13.164
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论文类别: Article
英文论文类别: Article
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