Enhanced leukemia cell detection using a novel magnetic needle and nanoparticles.
Enhanced leukemia cell detection using a novel magnetic needle and nanoparticles.
复制标题
DOI：
10.1158/0008-5472.can-09-1083
复制
发表时间：
2009-11-01
期刊：
影响因子：
11.2
通讯作者：
Larson RS
中科院分区：
文献类型：
--
作者：
Jaetao JE;Butler KS;Adolphi NL;Lovato DM;Bryant HC;Rabinowitz I;Winter SS;Tessier TE;Hathaway HJ;Bergemann C;Flynn ER;Larson RS
急性白血病是一种造血系统恶性肿瘤，其微小残留病的准确测量对于确定预后和治疗至关重要。虽然骨髓穿刺和光学显微镜检查仍然是目前检测残留疾病的护理标准，但这些方法不能可靠地区分少于5%的淋巴母细胞。为了改善骨髓中白血病细胞的检测，我们开发了一种新的装置，该装置采用与超顺磁性氧化铁纳米颗粒（SPION）结合的抗体，并直接针对急性白血病抗原CD34，再加上“磁针”活检。将表达高或低水平CD34的白血病细胞系与抗CD34偶联SPION孵育。三个独立的方法，包括显微镜，超导量子干涉仪（SQUID）磁力测定，并在体外磁针提取，然后评估细胞采样。我们发现，CD34结合的纳米颗粒优先结合高表达CD34的细胞系。此外，磁针能够识别稀释到正常血液中的细胞系和患者白血病细胞，其浓度低于缓解期骨髓样本中通常发现的浓度。最后，在接近微小残留病的新鲜骨髓穿刺样本中，磁针增强了光学显微镜可检测到的淋巴母细胞百分比10倍。这些数据表明，使用抗原靶向磁性纳米颗粒和磁针进行骨髓活检，用于评估CD 34阳性急性白血病的微小残留病，与目前的护理标准相比，可以显著提高灵敏度。
Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. While bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that employs antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) and directed against the acute leukemia antigen CD34, coupled with a “magnetic needle” biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34-conjugated SPIONs. Three separate approaches including microscopy, Superconducting Quantum Interference Device (SQUID) magnetometry, and in vitro magnetic needle extraction were then employed to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by ten-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared to the current standard of care.