期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 167, 期 5, 页码 587-599出版社
WILEY
DOI: 10.1111/bjh.13096
关键词
trisomy 21; Down syndrome acute lymphoblastic leukaemia; acute megakaryoblastic leukaemia; transient abnormal myelopoiesis; GATA1
类别
资金
- Leukaemia Lymphoma Research
- Children with Cancer
- Kay Kendall Leukaemia Fund
- Leuka
- Israel Science Foundation Legacy program
- Israel Science Foundation iCORE program
- US-Israel Bi-national Science Foundation
- Israel Cancer Research Foundation
- WLBH Foundation
- Waxman Foundation
- Swiss Bridge Foundation
- German Israeli Foundation
- Shapiro Chair of haematological malignancies in Tel Aviv University
- Medical Research Council [MC_UU_12009/14] Funding Source: researchfish
- MRC [MC_UU_12009/14] Funding Source: UKRI
Children with constitutional trisomy 21 (cT21, Down Syndrome, DS) are at a higher risk for both myeloid and B-lymphoid leukaemias. The myeloid leukaemias are often preceded by a transient neonatal pre-leukaemic syndrome, Transient Abnormal Myelopoiesis (TAM). TAM is caused by cooperation between cT21 and acquired somatic N-terminal truncating mutations in the key haematopoietic transcription factor GATA1. These mutations, which are not leukaemogenic in the absence of cT21, are found in almost one-third of neonates with DS. Analysis of primary human fetal liver haematopoietic cells and of human embryonic stem cells demonstrates that cT21 itself substantially alters human fetal haematopoietic development. Consequently, many haematopoietic developmental defects are observed in neonates with DS even in the absence of TAM. Although studies in mouse models have suggested a pathogenic role of deregulated expression of several chromosome 21-encoded genes, their role in human leukaemogenesis remains unclear. As cT21 exists in all embryonic cells, the molecular basis of cT21-associated leukaemias probably reflects a complex interaction between deregulated gene expression in haematopoietic cells and the fetal haematopoietic microenvironment in DS.
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