Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin
| Autor: | Yurong Tan, Megan A. Hatlen, Na Man, Nolan Chastain, Feng Chun Yang, Mengyao Sheng, Stephen D. Nimer, Haiming Xu, Marta Garcia-Cao, Ronit Shah, Xiao-Jian Sun, Lan Wang, Gang Huang, Junhong Song, Guoyan Cheng, Fan Liu, Yuan Zhou, Robert Benezra, Na Liu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21 Inhibitor of Differentiation Protein 1 Oncogene Proteins Fusion Cell of origin Immunology Biology Biochemistry 03 medical and health sciences Mice Inside BLOOD Commentary hemic and lymphatic diseases Cell Line Tumor medicine Animals Humans neoplasms Mice Knockout Fetus Myeloid leukemia Cell Biology Hematology Neoplasms Experimental Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Fusion protein Transplantation Leukemia 030104 developmental biology medicine.anatomical_structure Cell culture Cancer research Bone marrow |
| Zdroj: | Blood. 127(19) |
| ISSN: | 1528-0020 |
| Popis: | 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(+) leukemia showed that Id1 expression is elevated in the former and reduced in the latter type of MLL-FP(+) AML. Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9-driven leukemia. |
| Databáze: | OpenAIRE |
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