mm.1s：多发性骨髓瘤的模型

It is estimated that in 2017 there will be about 30,000 new cases diagnosed and about 13,000 patient deaths from multiple myeloma. However, it is a relatively uncommon type of cancer with a lifetime risk of 1 in 143 (0.7%). The risk of being diagnosed with multiple myeloma increases as people age, with the majority of people being diagnosed at age 65 or older. Men are slightly more likely to develop multiple myeloma than women and African Americans are twice as likely to develop this type of cancer. However, the greatest risk factor for begin diagnosed with multiple myeloma is already having a plasma cell disease. Patients with monoclonal gammopathy of undetermined significance (MGUS) or solitary plasmacytoma will eventually develop multiple myeloma.

多发性骨髓瘤是一种克隆B细胞恶性肿瘤，其特征在于骨髓中末端分化的抗体产生血浆细胞的积累。骨髓瘤细胞内的遗传突变及其与各种细胞因子和生长因子的相互作用有助于疾病的侵袭和增强的耐药性。患者一般是无症状的直至非常晚期疾病。一旦发现疾病，骨骼中的定位，特别是脊柱，是常见的。目前，黄金标准疗法是多柔比星和地塞米松的组合与硼替佐米。Bortezomib的添加改善了接近50％的整体反应速率。¹

一种常用的细胞系来评估多个骨髓瘤的新疗法是mm.1s。MM.1S来自42岁的非洲裔美国女性，并被记录在明确CD25，CD38，CD52和CD59。它还表达了糖皮质激素受体，是地塞米松的敏感性。²为了更有效地监控体内疾病进展，Covance用荧光素酶（mm.1s-pmmp-lucneo）转染mm.1s系列。通过生物发光成像（BLI），我们可以通过时间监测易溶性疾病进展，并找到可重复的体内小鼠的生长（图1和图2）。

在SCID米色老鼠,中位数doubli肿瘤体积ng time is ~2 days (Figure 3), and median time to morbidity/mortality endpoint is 35-45 days. To further optimize the MM.1S-pMMP-LucNeo model, we characterized growth in the NSG mouse strain which shows more aggressive disease onset (staging seven days post implant vs. 15 days in SCID mice). In NSG mice, the tumor volume doubling time is ~1.8 days (Figure 4) and median time to endpoint is ~21 days, roughly half the overall survival time observed in the SCID beige mouse.

在我们调查的所有小鼠品系中，动物在整个研究期间相对无症状，仅在疾病晚期出现症状（图5和图6）；类似于这种疾病在人类身上的表现。小鼠常见的晚期临床症状包括嗜睡和瘫痪。这些动物的BLI显示了信号在脊柱、长骨和下颌骨的定位。单药硼替佐米（Velcade^®)在这个模型中对疾病进展的影响有限。这与临床数据相似，临床数据表明硼替佐米与其他药物联合应用可改善治疗反应。考虑到模型的可重复性以及疾病进展和反应的转化方面，MM.1S模型为评估新的单药治疗以及药物组合提供了平台。