期刊
BLOOD
卷 119, 期 12, 页码 2873-2882出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-08-370981
关键词
-
类别
资金
- National High Tech Program for Biotechnology [863:2012AA02A505]
- Chinese National Key Basic Research Project [973: 2010CB529200]
- Mega-projects of Science Research for the 10th Five-Year Plan [2008ZX09312-026]
- National Natural Science Foundation of China [30830119, 30821063]
- Samuel Waxman Cancer Research Foundation
The BCR-ABL fusion protein generated by t(9;22)(q34;q11) in chronic myeloid leukemia (CML) plays an essential role in the pathogenesis of the myeloproliferative disorder status at the chronic phase of the disease, but progression from the chronic phase to blast crisis (BC) is believed to require additional mutations. To explore the underlying mechanisms for BC, which is characterized by a blockage of blood cell differentiation, we screened several genes crucial to hematopoiesis and identified 10 types of mutations in RUNX1 among 11 of 85 (12.9%) patients with acute transformation of CML. Most of the mutations occurred in the runt homology domain, including H78Q, W79C, R139G, D171G, R174Q, L71fs-ter94, and V91fs-ter94. Further studies indicated that RUNX1 mutants not only exhibited decreased transactivation activity but also had an inhibitory effect on the WT RUNX1. To investigate the leukemogenic effect of mutated RUNX1, H78Q and V91fs-ter94 were transduced into 32D cells or BCRABL-harboring murine cells, respectively. Consistent with the myeloblastic features of advanced CML patients with RUNX1 mutations, H78Q and V91fs-ter94 disturbed myeloid differentiation and induced a BC or accelerated phase-like phenotype in mice. These results suggest that RUNX1 abnormalities may promote acute myeloid leukemic transformation in a subset of CML patients. (Blood. 2012; 119(12):2873-2882)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据