Xishan Zhu, Xu Zhou, Lawei Yang, Gang Liu
Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Guangdong, P.R. China.
Clin Lab. 2012;58(7-8):607-13.
Overwhelming evidence from Chronic Myeloid Leukemia (CML) research indicates that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated.
Here we isolated fetal liver kinase-1-positive (Flk1+) cells from CML patients and we tested their biological characteristics. In addition, endothelial and hematopoietic differentiation assays were also performed to test their cancer stem cell ability.
We found these cells expressed the BCR/ABL specific CML oncogene. Co-culture assay also indicated they could promote HSC blast colonies. Further studies showed they could differentiate not only into endothelial lineages but also into erythroid cells at the single-cell level.
Fetal bone marrow-derived Flk1+CD34- multipotent stem cells have the capacity for self-renewal and multilineage differentiation even after being expanded for more than 50 cell doublings, they might be the cancer stem cells and a target source in the treatment of CML.
慢性髓性白血病（CML）研究的大量证据表明，患者体内存在导致急变期的静止性CML干细胞。虽然早在30多年前就首次提出CML起源于造血干细胞（HSC），但最近也在研究HSC以外的CML起始细胞。
我们从CML患者中分离出胎儿肝激酶1阳性（Flk1+）细胞，并测试了它们的生物学特性。此外，还进行了内皮和造血分化试验，以测试它们的癌症干细胞能力。
我们发现这些细胞表达BCR/ABL特异性CML癌基因。共培养试验还表明它们可以促进HSC原始细胞集落。进一步研究表明，它们不仅可以在单细胞水平上分化为内皮谱系，还可以分化为红细胞。
胎儿骨髓来源的Flk1+CD34-多能干细胞即使在扩增超过50次细胞倍增后仍具有自我更新和多谱系分化能力，它们可能是癌症干细胞和CML治疗的靶标来源。
