Expression of CD25 fluctuates in the leukemia-initiating cell population of CD25-positive AML
Expression of CD25 fluctuates in the leukemia-initiating cell population of CD25-positive AML
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DOI：
10.1371/journal.pone.0209295
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发表时间：
2018-12-14
期刊：
影响因子：
3.7
通讯作者：
Katayama, Naoyuki
中科院分区：
文献类型：
--
作者：
Kageyama, Yuki;Miwa, Hiroshi;Katayama, Naoyuki
10-20%的急性髓性白血病（AML）患者在白血病细胞上表达CD25，其表达与预后不良相关。我们使用患者来源的异种移植模型重新评估了CD25表达与AML白血病起始细胞（LIC）特性之间的关系。我们将来自cd25阳性AML的谱系标记阴性（Lin(-)） CD34(+)CD38（-）或Lin(-)CD34（+）细胞分为cd25阳性和阴性群体，然后将每个群体移植到NOD中。Cg-Prkde (scid) Il2rg (tm1Wjl) /深圳老鼠。在9例cd25阳性AML患者中的3例中，cd25阳性和cd25阴性人群均观察到白血病移植。在这三名患者中的两名，在初次移植时移植的cd25阳性和阴性的Lin(-)CD34（+）细胞导致二次移植时的白血病植入，其中植入的细胞含有cd25阳性和阴性的Lin(-)CD34(+) AML细胞。在体外培养系统中，CD25在来自两例CD25阳性AML的Lin(-)CD34（+）细胞的CD25阴性群体中被显著诱导表达。在一个病例中，cd25阳性的Lin(-)CD34（+）细胞产生cd25阴性和-阳性的CD34（+）细胞。这些观察结果表明，在患者来源的异种移植模型中，存在CD25阳性和CD25阴性的群体，可以重建CD25阳性的AML，并且CD25表达在AML的LICs中波动。
CD25 is expressed on leukemic cells in 10-20% cases of acute myeloid leukemia (AML), and its expression is associated with poor prognosis. We reevaluated the relationship between CD25 expression and the leukemia-initiating cell (LIC) properties of AML using a patient-derived xenograft model. We divided lineage marker-negative (Lin(-)) CD34(+)CD38(-) or Lin(-)CD34(+) cells from CD25-positive AML into CD25-positive and -negative populations, and then transplanted each population into NOD.Cg-Prkde(scid)Il2rg(tm1Wjl)/Sz mice. Leukemic engraftment was observed with both CD25-positive and -negative populations from three of nine CD25-positive AML patients. In two of those three patients, CD25-positive and -negative Lin(-)CD34(+) cells engrafted at the primary transplantation led to leukemic engraftment at the secondary transplantation, in which engrafted cells contained both CD25-positive and -negative Lin(-)CD34(+) AML cells. In an in vitro culture system, expression of CD25 was considerably induced in the CD25-negative population of Lin(-)CD34(+) cells from two cases of CD25-positive AML. In one case, CD25-positive Lin(-)CD34(+ )cells gave rise to CD25-negative as well as -positive CD34(+) cells. These observations suggest that there exist CD25-positive and -negative populations that can reconstitute CD25-positive AML in a patient-derived xenograft model, and that CD25 expression fluctuates in the LICs of AML.