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

Abstract:

: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.

journal_name

Haematologica

journal_title

Haematologica

authors

Liu X,Ma Y,Li R,Guo D,Wang N,Zhao Y,Yin J,Ren Q,Lin Y,Ma X

doi

10.3324/haematol.2018.190652

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1969-1979

issue

12

eissn

0390-6078

issn

1592-8721

pii

haematol.2018.190652

journal_volume

103

pub_type

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