Stem-like tumor cells confer drug resistant properties to mantle cell lymphoma
Stem-like tumor cells confer drug resistant properties to mantle cell lymphoma
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DOI：
10.3109/10428194.2011.562570
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发表时间：
2011-06-01
影响因子：
2.6
通讯作者：
McCarty, Nami
中科院分区：
文献类型：
--
作者：
Jung, Hyun Joo;Chen, Zheng;McCarty, Nami
我们最近在人类套细胞淋巴瘤（MCL）（非霍奇金淋巴瘤（NHL）的一种特别致命的亚型）中发现了克隆性恶性干细胞群。我们发现，CD 45 + CD 19- MCL细胞，我们称之为MCL起始细胞（MCL-IC），具有高度致瘤性，并在体内显示自我更新能力;相反，CD 45 + CD 19 + MCL细胞，构成肿瘤内的绝大多数细胞，没有自我更新能力，致瘤性大大降低。鉴于癌症起始细胞在癌症耐药性中的新认识，研究CD 45 + CD 19-MCL-IC是否在人类MCL的耐药性中发挥作用至关重要。我们发现，与CD 45 + CD 19+细胞相比，MCL-IC对临床相关化疗药物的联合或单一方案更具耐药性，这种耐药性主要是由于富含ABC转运蛋白的静止特性。总之，设计新的治疗方法来杀死CD 45 + CD 19-MCL-IC可以防止复发并增加患者生存率。
We recently identified clonogenic malignant stem cell populations in human mantle cell lymphoma (MCL), a particularly deadly subtype of non-Hodgkin lymphoma (NHL). We discovered that CD45+CD19- MCL cells, which we termed MCL-initiating cells (MCL-ICs), are highly tumorigenic and display self-renewal capacity in vivo; in contrast, CD45+CD19+ MCL cells, which constitute the vast majority of cells within the tumors, show no self-renewal capacity and greatly reduced tumorigenicity. Given the newly appreciated role of cancer-initiating cells in the drug resistance of cancers, it is critical to investigate whether CD45+CD19- MCL-ICs play a role in the drug resistance of human MCL. We discovered that MCL-ICs were more resistant to clinically relevant chemotherapeutic agents, in combination or in a single regimen, compared to CD45+CD19+ cells, and that this drug resistance was largely due to quiescent properties with enriched ABC transporters. In conclusion, designing novel therapies to kill CD45+CD19- MCL-ICs may prevent relapse and increase patient survival.