Single cell growth assay for residual cells in acute lymphoblastic leukemia

 描述（由申请人提供）：我们的申请对血液系统癌症有广泛的影响，但我们的具体重点是急性淋巴细胞白血病。监测微小残留病（MRD）具有预后价值的证据越来越强，然而，许多患者的深度临床反应和治愈之间的主要障碍是无法治疗靶向MRD。我们建议扩大和验证一种新型的微流体系统，该系统在特定治疗之前和之后以前所未有的精度监测MRD样品中单个细胞的质量。该R33应用程序的主要可交付成果是一个可用于临床研究的系统，以解决以下问题：在MRD时获得的患者癌细胞对特定疗法的生长反应是否可预测该疗法对该患者的疗效？目前，细胞毒性治疗只是针对持续性MRD患者进行强化治疗，而不是选择性地使用已知对特定患者最有效的治疗方法。我们通过直接测量细胞生长来测定MRD的治疗敏感性的方法将代表在利用MRD的存在治疗白血病方面的显著进步。

 DESCRIPTION (provided by applicant): Our application has broad implications for hematologic cancers but our specific focus will be on acute lymphoblastic leukemias. Evidence that monitoring minimal residual disease (MRD) has prognostic value is becoming increasingly strong, however the primary roadblock between deep clinical response and cure for many patients has been the inability to therapeutically target MRD. We are proposing to scale-up and validate a novel microfluidic system that monitors the mass of individual cells within an MRD sample with unprecedented precision before and after delivery of a particular treatment. The primary deliverable of this R33 application is a system that can be used in clinical studies to address the following question: Does the growth response of a patient's cancer cells obtained at the time of MRD to a particular therapy predict that therapy's efficacy for that patient? At present, cytotoxic therapy is simply intensified for patients with persistent MRD, rather than selectivity targeting it with a therapy known to be most effective for a particular patient. Our approach of assaying MRD for therapeutic sensitivity by a direct measure of cell growth would represent a significant advance in utilizing the presence of MRD in the treatment of leukemia.