Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome

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• 作者：Denise K. Holmes ; Nicola Bates ; Mary Murray ; E.J. Ladusans ; Antonino Morabito ; Paula H.B. Bolton-Maggs ; Tracey A. Johnston ; Steve Walkenshaw ; Robert F. Wynn ; Ilaria Bellantuono
• 刊名：Experimental Hematology
• 出版年：2006
• 出版时间：December 2006
• 年：2006
• 卷：34
• 期：12
• 页码：1611-1615
• 全文大小：440 K

文摘

Objectives

There is an increased risk of myeloid malignancy in individuals with Down's syndrome (DS), which is associated with a mutation in exon 2 of the transcription factor GATA-1. It is recognized that there is accelerated telomere shortening in blood cells of children with DS similar to that in conditions such as Fanconi anemia and dyskeratosis congenita. The latter conditions are associated with stem cell deficiency and clonal change, including acute myeloid leukemia. In this study we address the questions 1) whether the accelerated telomere shortening is associated with progenitor/stem cell deficiency in individuals with DS, predisposing to clonal change and 2) whether the occurrence of reduced numbers of stem/progenitor cells precede the incidence of mutations in exon 2 of GATA-1.

Material and methods

Peripheral blood from fetuses (23–35 weeks gestation) and/or bone marrow from children affected by DS and age-matched hematologically healthy controls were analyzed for telomere length, content of stem/progenitor cells, and mutations in exon 2 of GATA-1.

Results

We found that hematopoietic stem/progenitor cell deficiency and telomere shortening occurs in individuals with DS in fetal life. Moreover, the presence of a low number of progenitor cells was not associated with mutations in exon 2 of GATA-1.

Conclusions

We propose that stem cell deficiency may be a primary predisposing event to DS leukemia development.