Institute of Internal Oncology, Center of Tumor Research and Therapy, Beijing Shijitan Hospital, Capital Medical University (the Ninth Medical College of Peking University), Beijing 100038, China.
Chin Med J (Engl). 2011 Aug;124(16):2423-30.
Overwhelming evidences on chronic myeloid leukemia (CML) indicate 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.
We have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Ph(+) patients with hemangioblast property. In this study, we isolated CML patient-derived Flk1(+)CD31(-)CD34(-) mesenchymal stem cells (MSCs) and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization (FISH) analysis, fluorescence activated cell sorting (FACS), enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors.
CML patient-derived Flk1(+)CD31(-)CD34(-) MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro.
CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells (HSCs). MSCs might be a potential target for developing efficacious treatment for CML.
大量关于慢性髓性白血病（CML）的证据表明，患者体内存在静止的 CML 干细胞，这些干细胞是导致急变期的原因。虽然 30 多年前就首次提出了 CML 的造血干细胞（HSC）起源，但最近也在研究 HSC 以外的 CML 起始细胞。
我们之前从 Ph（+）伴血管母细胞瘤特性患者的骨髓中分离出具有 BCR/ABL 融合基因的胎肝激酶-1 阳性（Flk1(+））细胞。在这项研究中，我们从 CML 患者中分离出 Flk1(+)CD31(-)CD34(-)间充质干细胞（MSC），并用荧光原位杂交（FISH）分析、荧光激活细胞分选（FACS）、酶联免疫吸附试验、混合淋巴细胞反应检测其生物学特性和免疫调节功能；然后我们将这些特征与健康供者进行比较。
CML 患者来源的 Flk1(+)CD31(-)CD34(-)MSC 具有正常的形态、表型和核型，但免疫调节功能受损。患者 Flk1(+)CD31(-)CD34(-)MSC 体外抑制 T 淋巴细胞活化和增殖的能力受损。
CML 患者来源的 MSC 具有受损的免疫调节功能，提示造血和免疫反应的失调可能起源于 MSC，而不是造血干细胞（HSC）。MSC 可能是开发有效治疗 CML 的潜在靶点。
