sciencemag.org SCIENCE IL L U S T R A T IO N : V . A L T O U N IA N / S C IE N C E K enneth Walsh was looking forward to a nice dinner and some interesting talks when he joined colleagues for a 2014 meeting of the venerable Medical Exchange Club in Boston. A cardiovascular biologist from Boston University’s School of Medicine, Walsh didn’t imagine that the presentations, on a peculiar blood cell imbalance, would have any relevance to his research. Then he saw the data. “I almost fell off my chair,” he says. The evening’s speakers, hematologist and oncologist Benjamin Ebert and molecular biologist Steven McCarroll, both of Harvard Medical School in Boston, revealed that the phenomenon, an excess growth of certain blood cells known as clonal hematopoiesis, is far more common than expected, affecting about 10% of people over the age of 70. Even more surprising, Ebert reported, was that the condition roughly doubles the odds of developing heart disease or suffering a stroke. Walsh had spent years studying how abnormal tissue growth in the circulatory system promotes cardiovascular disease. But the talks that evening galvanized him to retool his lab to probe the connection between clonal hematopoiesis and heart disease. Earlier this year, his group reported its first results, revealing a potential mechanism through which clonal hematopoiesis might help clog our arteries. Walsh isn’t the only researcher fascinated by the phenomenon, which is emerging as an almost universal companion of aging—and may be far more widespread than even Ebert and McCarroll estimated 3 years ago. “Clonal hematopoiesis is probably going to happen to all of us if we get old enough,” says geneticist Kári Stefánsson, CEO of deCODE genetics in Reykjavik who has studied its prevalence. In recent years, researchers have pinpointed some of the mutations that spur the condition, and now they’re uncovering evidence that clonal hematopoiesis may be harming our health in multiple ways, by boosting the odds not just of heart disease but of leukemia and many other conditions as well.

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杀手克隆

sciencemag.org SCIENCE IL LUSTRAT IO N：V。ALTOUN I N / SC IE NCEK enneth Walsh 在与同事们一起参加 2014 年在波士顿举行的著名医学交流俱乐部会议时，期待着享用一顿丰盛的晚餐和一些有趣的谈话。波士顿大学医学院的心血管生物学家 Walsh 没想到这些关于特殊血细胞失衡的演讲与他的研究有任何关联。然后他看到了数据。“我差点从椅子上掉下来，”他说。当晚的演讲者、波士顿哈佛医学院的血液学家和肿瘤学家本杰明·艾伯特和分子生物学家史蒂文·麦卡罗尔透露，这种称为克隆造血的某些血细胞过度生长的现象比预期的要普遍得多，影响了大约 10 70 岁以上人口的百分比。埃伯特报告说，更令人惊讶的是，这种情况大约使患心脏病或中风的几率增加了一倍。沃尔什花了数年时间研究循环系统中的异常组织生长如何促进心血管疾病。但那天晚上的谈话激励他重新配置他的实验室，以探索克隆性造血和心脏病之间的联系。今年早些时候，他的小组报告了第一个结果，揭示了克隆造血可能有助于堵塞动脉的潜在机制。沃尔什并不是唯一对这种现象着迷的研究人员，这种现象几乎是衰老的普遍伴侣——而且可能比 3 年前 Ebert 和 McCarroll 估计的更普遍。“如果我们变老，克隆造血可能会发生在我们所有人身上，”遗传学家 Kári Stefánsson 说，他是雷克雅未克 deCODE 遗传学公司的首席执行官，他研究了其患病率。近年来，研究人员已经确定了一些导致这种情况的突变，现在他们发现了克隆造血可能以多种方式危害我们的健康的证据，不仅增加了心脏病的几率，而且增加了白血病和许多其他疾病的几率。条件也一样。