TY - JOUR AU - Xiaoyan Liu, AU - Yanping Ma, AU - Rongrong Li, AU - Dan Guo, AU - Nan Wang, AU - Yangyang Zhao, AU - Jing Yin, AU - Qian Ren, AU - Yongmin Lin, AU - Xiaotong Ma, PY - 2018/11/30 Y2 - 2024/03/29 TI - Niche TWIST1 is critical for maintaining normal hematopoiesis and impeding leukemia progression JF - Haematologica JA - haematol VL - 103 IS - 12 SE - Articles DO - 10.3324/haematol.2018.190652 UR - https://haematologica.org/article/view/8692 SP - 1969-1979 AB - The bone marrow microenvironment regulates normal and malignant hematopoiesis, but the underlying molecular mechanisms remain poorly defined. Using a chimeric mice model, we demonstrate that Twist1 deletion in the bone marrow microenvironment results in alteration of multiple niche cells as well as downregulated expression of major hematopoietic stem cell supportive factors. The perturbed microenvironment reduces hematopoietic stem cell homing and retention, impairs hematopoietic stem cell self-renewal and induces myeloid skewing. Nevertheless, it accelerates the progression of MLL-AF9 leukemia, which is partially mediated by Jagged-2-dependent Notch signaling. Our data provide the first demonstration of a pivotal role of TWIST1 in favoring normal hematopoiesis and hampering leukemia development. They also bring new insights into the role of the bone marrow niche in driving the development of acute myeloid leukemia, and suggest possible new avenues, exploiting the niche, to improve leukemia treatments. ER -