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Publication : Niche TWIST1 is critical for maintaining normal hematopoiesis and impeding leukemia progression.

First Author  Liu X Year  2018
Journal  Haematologica Volume  103
Issue  12 Pages  1969-1979
PubMed ID  30026340 Mgi Jnum  J:313192
Mgi Id  MGI:6791570 Doi  10.3324/haematol.2018.190652
Citation  Liu X, et al. (2018) Niche TWIST1 is critical for maintaining normal hematopoiesis and impeding leukemia progression. Haematologica 103(12):1969-1979
abstractText  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.
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