期刊
CELL REPORTS
卷 20, 期 3, 页码 572-585出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.06.067
关键词
-
类别
资金
- National Health and Medical Research Council (NHMRC)
- Leukaemia Foundation
- Anthony Rothe Foundation
- Cancer Institute for New South Wales
- South Eastern Area Laboratory Services (SEALS)
- Wellcome Trust
- Leukemia and Lymphoma Society, Medical Research Council (UK)
- Swedish Cancer Society
- Cancer Society in Stockholm
- Swedish Research Council, Bloodwise UK
- NIHR Biomedical Research Centre, Oxford
- Cancer Research UK
- Versus Arthritis [21019] Funding Source: researchfish
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only similar to 50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin alpha 5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders.
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