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Cell:新方法靶向阻止致命的儿童白血病

2017-01-07 佚名 生物谷

在一项新的研究中,来自美国西北大学费恩柏格医学院的研究人员发现一种罕见的致命性儿童白血病的基因促发物,并且鉴定出一种阻止白血病细胞增殖的靶向分子疗法。相关研究结果于2017年1月5日在线发表在Cell期刊上,论文标题为“Therapeutic Targeting of MLL Degradation Pathways in MLL-Rearranged Leukemia”。 混合谱系白血病(m


在一项新的研究中,来自美国西北大学费恩柏格医学院的研究人员发现一种罕见的致命性儿童白血病的基因促发物,并且鉴定出一种阻止白血病细胞增殖的靶向分子疗法。相关研究结果于2017年1月5日在线发表在Cell期刊上,论文标题为“Therapeutic Targeting of MLL Degradation Pathways in MLL-Rearranged Leukemia”。

混合谱系白血病(mixed lineage leukemia, MLL)主要影响新生儿和婴儿。在被确诊后,不到10%~20%的MLL儿童存活的时间不会超过5年。美国每年有300例MLL产生。

论文通信作者、西北大学费恩柏格医学院生物化学与分子遗传学教授、儿科教授Ali Shilatifard说,“在过去20年,我们一直在实验室中尝试着在分子水平上理解MLL易位如何导致儿童患上这种罕见的严重性的白血病以至于我们能够利用这种信息开发一种有效地治疗这种癌症的方法。如今,我们取得一项至关重要的突破。”

Shilatifard、他的研究生Kevin Liang和他们的同事们对这项突破极其充满期待,并且正在试图将他们的发现转化为治疗儿童白血病的方法。

Liang说,“当存在错误的11号染色体在MLL 基因位置上发生断裂,与19号染色体等其他的染色体融合在一起时,混合谱系白血病就会产生。这种突变会产生一种促进白血病致病过程的蛋白。”

大多数与这种癌症相关的研究着重关注存在错误的11号染色体拷贝。但是人体存在两个拷贝的11号染色体,因此Shilatifard团队想要研究野生型11号染色体拷贝。他们发现患上儿童白血病的单个细胞含有极其低水平的由野生型MLL基因产生的蛋白。Shilatifard和Liang推断如果他们能够提高野生型MLL蛋白的水平,那么它将会替换促进癌症产生的突变蛋白版本,从而可能治愈这种白血病。

通过开展详细的分子筛选和生化筛选,Shilatifard团队鉴定出一种让野生型MLL蛋白保持稳定和干扰白血病促发性蛋白突变体的化合物。为了测试它的有效性,通过与西北大学John Crispino团队合作,他们在体外培养MLL细胞,并且将它们移植到小鼠体内。他们随后将这种化合物注射到这些小鼠体内。所获得的结果是野生型MLL蛋白反弹到健康的水平,而且这些白血病细胞不能够像之前那样快速地生长。

西北大学研究人员如今正在合成更好的化合物。他们希望最终在芝加哥发起一项I期临床试验来测试这些化合物。

原始出处

Kaiwei Liang, Andrew G. Volk, Jeffrey S. Haug, Stacy A. Marshall, Ashley R.et.al.Therapeutic Targeting of MLL Degradation Pathways in MLL-Rearranged Leukemia.Cell.2016

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    2017-01-28 维他命
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    2017-01-11 Jackie Li

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    2017-01-11 Jackie Li

    收藏

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    2017-01-10 虈亣靌

    机遇啊!看来不久的将来又有新技术要诞生了。

    0

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