T memory stem cells are the hierarchical apex of adult T-cell leukemia
T memory stem cells are the hierarchical apex of adult T-cell leukemia
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DOI：
10.1182/blood-2014-10-607465
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发表时间：
2015-06-04
期刊：
影响因子：
20.3
通讯作者：
Takaori-Kondo, Akifumi
中科院分区：
文献类型：
--
作者：
Nagai, Yuya;Kawahara, Masahiro;Takaori-Kondo, Akifumi
成人T细胞白血病（ATL）是由人类T细胞白血病病毒1型（HTLV-1）引起的外周CD 4（+）T细胞肿瘤。尽管使用人类标本和小鼠模型进行了一些研究，但ATL细胞的确切起源仍不清楚。在这里，我们提供了一个新的见解ATL细胞的层次结构。HTLV-1感染的细胞和显性ATL克隆被成功地追溯到CD 45 RA（+）T记忆干细胞（T-SCM），其最近被鉴定为具有干细胞性质的独特群体，尽管大多数ATL细胞是CD 45 RA（-）CD 45 RO（+）常规记忆T细胞。来自ATL患者的T-SCM细胞能够以较低的增殖模式维持自身，并在快速繁殖阶段分化为其他记忆T细胞群。在异种移植模型中，少量的T-SCM细胞有效地重新填充相同的ATL克隆并补充下游CD 45 RO（+）记忆T细胞，而其他群体则没有这种能力。综上所述，这些发现表明ATL细胞的表型和功能异质性以及层次结构。T-SCM细胞被鉴定为能够重建相同ATL克隆的分级顶点。因此，这是第一个报告，以证明与T-SCM细胞的T细胞恶性肿瘤的关联。
Adult T-cell leukemia (ATL) is a peripheral CD4(+) T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). Despite several investigations using human specimens and mice models, the exact origin of ATL cells remains unclear. Here we provide a new insight into the hierarchical architecture of ATL cells. HTLV-1-infected cells and dominant ATL clones are successfully traced back to CD45RA(+) T memory stem (T-SCM) cells, which were recently identified as a unique population with stemlike properties, despite the fact that the majority of ATL cells are CD45RA(-)CD45RO(+) conventional memory T cells. T-SCM cells from ATL patients are capable of both sustaining themselves in less proliferative mode and differentiating into other memory T-cell populations in the rapidly propagating phase. In a xenograft model, a low number of T-SCM cells efficiently repopulate identical ATL clones and replenish downstream CD45RO(+) memory T cells, whereas other populations have no such capacities. Taken together, these findings demonstrate the phenotypic and functional heterogeneity and the hierarchy of ATL cells. T-SCM cells are identified as the hierarchical apex capable of reconstituting identical ATL clones. Thus, this is the first report to demonstrate the association of a T-cell malignancy with T-SCM cells.