Zhang Liangxuan, Beasley Sharon, Prigozhina Natalie L, Higgins Renee, Ikeda Shoji, Lee Florence Y, Marrinucci Dena, Jia Shidong
Departments of Oncology Biomarker Development, Genentech Inc, South San Francisco, CA, USA.
Epic Sciences Inc., San Diego, CA, USA.
J Circ Biomark. 2016 Jan 1;5:10. doi: 10.5772/64124. eCollection 2016 Jan-Dec.
Multiple myeloma (MM) remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs) in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM) biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease management and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluorescence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs) on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6) as a readout for PI3K/AKT pathway activation. Clinical feasibility of the assay was established by testing blood samples from a small cohort of patients, where we detected populations of both CD138 and CD138 MM CTCs. this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.
尽管近期治疗方法有所改进,但多发性骨髓瘤(MM)仍然是一种无法治愈的疾病。在外周血中检测和鉴定MM循环肿瘤细胞(CTC)的能力提供了一种替代方法,通过简单的采血来取代或补充侵入性骨髓(BM)活检,提供实时、临床相关信息,从而改善疾病管理和治疗选择。在此,我们开发并验证了一种无需富集的基于细胞的免疫荧光MM CTC检测方法,该方法利用自动数字病理算法,根据CD138和CD45表达水平以及一些形态学参数,将MM CTC与白细胞(WBC)区分开来。这些MM CTC进一步被鉴定为磷酸化核糖体蛋白S6(pS6)的表达,作为PI3K/AKT途径激活的读数。通过检测一小群患者的血样确定了该检测方法的临床可行性,在这些血样中我们检测到了CD138和CD138 MM CTC群体。在本研究中,我们开发了一种基于免疫荧光细胞的检测方法来检测和鉴定MM中的CTC。