冰島雷克雅未克2023年11月7日 /美通社/ -- Amgen 子公司 deCODE genetics 今天在《自然-遺傳學》上發表了一篇綜合性新研究，對克隆性造血的流行病學、體細胞和種系遺傳學進行了深入探討。采用來自冰島和英國生物庫的全基因組序列數據，結合獨特的體細胞突變條碼策略，對克隆性造血系統疾病進行了大規模的人群研究。

《克隆性造血的流行病學和遺傳學——惡性 前造血干細胞疾病》論文的第一作者 deCODE genetics 科學家 Simon N. Stacey 與 deCODE genetics 的(de)行政總裁(cai) Kari Stefánsson 進行了交流。

克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)是指(zhi)(zhi)當造(zao)(zao)(zao)(zao)血(xue)(xue)干細(xi)(xi)(xi)(xi)胞(bao) (HSC) 的(de)(de)(de)(de)(de)(de)(de)(de)(de)一個(ge)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)譜系擴增(zeng)(zeng)(zeng)(zeng)并成為(wei)(wei)(wei)大(da)部(bu)(bu)分(fen)(fen)(fen)(fen)成熟血(xue)(xue)細(xi)(xi)(xi)(xi)胞(bao)的(de)(de)(de)(de)(de)(de)(de)(de)(de)來(lai)(lai)源時(shi)(shi)出現(xian)的(de)(de)(de)(de)(de)(de)(de)(de)(de)一種情(qing)況(kuang)。deCODE 的(de)(de)(de)(de)(de)(de)(de)(de)(de)科學家采用了(le)(le)(le)(le)(le)來(lai)(lai)自(zi) 176000 人的(de)(de)(de)(de)(de)(de)(de)(de)(de)全(quan)(quan)基因組序列數(shu)(shu)據(ju)(ju)，來(lai)(lai)檢(jian)測(ce)(ce)在(zai)(zai)(zai)(zai)(zai)超過(guo) 16000 個(ge)對(dui)象中(zhong)(zhong)的(de)(de)(de)(de)(de)(de)(de)(de)(de)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)情(qing)況(kuang)。該研(yan)(yan)究(jiu)再(zai)次(ci)確認了(le)(le)(le)(le)(le)老年人中(zhong)(zhong)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)異(yi)(yi)常(chang)的(de)(de)(de)(de)(de)(de)(de)(de)(de)高(gao)(gao)發率（在(zai)(zai)(zai)(zai)(zai) 80 歲以(yi)(yi)上的(de)(de)(de)(de)(de)(de)(de)(de)(de)人群中(zhong)(zhong)接(jie)近 50%）。存(cun)在(zai)(zai)(zai)(zai)(zai)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)患(huan)(huan)者(zhe)后續被診斷為(wei)(wei)(wei)血(xue)(xue)液系統腫(zhong)瘤(liu)的(de)(de)(de)(de)(de)(de)(de)(de)(de)風險(xian)更高(gao)(gao)，并且其(qi)(qi)死(si)亡(wang)率也(ye)相(xiang)(xiang)(xiang)(xiang)對(dui)較高(gao)(gao)。克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)以(yi)(yi)前(qian)被認為(wei)(wei)(wei)與(yu)多(duo)(duo)種非(fei)血(xue)(xue)液學疾(ji)(ji)病相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)，包(bao)括癌癥和(he)心血(xue)(xue)管疾(ji)(ji)病等。然(ran)而，研(yan)(yan)究(jiu)表明(ming)(ming)，吸(xi)(xi)煙(yan)(yan)行為(wei)(wei)(wei)可(ke)能(neng)(neng)以(yi)(yi)劑(ji)量(liang)依賴(lai)的(de)(de)(de)(de)(de)(de)(de)(de)(de)方(fang)式(shi)加速(su)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)進展，與(yu)所(suo)有(you)(you)(you)(you)(you)相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)的(de)(de)(de)(de)(de)(de)(de)(de)(de)非(fei)血(xue)(xue)液疾(ji)(ji)病可(ke)能(neng)(neng)存(cun)在(zai)(zai)(zai)(zai)(zai)相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)性(xing)(xing)(xing)(xing)(xing)。該研(yan)(yan)究(jiu)發現(xian)了(le)(le)(le)(le)(le) HSC 發生突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)的(de)(de)(de)(de)(de)(de)(de)(de)(de)證(zheng)據(ju)(ju)，這(zhe)些(xie)(xie)(xie)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)可(ke)驅動其(qi)(qi)株落增(zeng)(zeng)(zeng)(zeng)殖。此(ci)(ci)外(wai)，研(yan)(yan)究(jiu)人員發現(xian)了(le)(le)(le)(le)(le) 25 種會(hui)(hui)(hui)讓個(ge)體(ti)(ti)更容易(yi)(yi)產生克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)遺(yi)傳(chuan)序列變(bian)(bian)異(yi)(yi)。deCODE 科學家們基于(yu)全(quan)(quan)基因組序列開發了(le)(le)(le)(le)(le)一種檢(jian)測(ce)(ce)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)方(fang)法。此(ci)(ci)種方(fang)法的(de)(de)(de)(de)(de)(de)(de)(de)(de)事實依據(ju)(ju)是，即每個(ge)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)體(ti)(ti)均攜帶一個(ge)獨特的(de)(de)(de)(de)(de)(de)(de)(de)(de)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)"條碼"，這(zhe)些(xie)(xie)(xie)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)在(zai)(zai)(zai)(zai)(zai)發育(yu)過(guo)程中(zhong)(zhong)產生，并在(zai)(zai)(zai)(zai)(zai)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)開始時(shi)(shi)存(cun)在(zai)(zai)(zai)(zai)(zai)于(yu)創始細(xi)(xi)(xi)(xi)胞(bao)中(zhong)(zhong)。如果具體(ti)(ti) HSC 克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)體(ti)(ti)充(chong)分(fen)(fen)(fen)(fen)增(zeng)(zeng)(zeng)(zeng)殖，那么就可(ke)以(yi)(yi)通過(guo)測(ce)(ce)序檢(jian)測(ce)(ce)到(dao)此(ci)(ci)類突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)條碼，這(zhe)提供了(le)(le)(le)(le)(le)患(huan)(huan)者(zhe)存(cun)在(zai)(zai)(zai)(zai)(zai)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)指(zhi)(zhi)示(shi)。克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)具有(you)(you)(you)(you)(you)許多(duo)(duo)癌前(qian)細(xi)(xi)(xi)(xi)胞(bao)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)增(zeng)(zeng)(zeng)(zeng)殖的(de)(de)(de)(de)(de)(de)(de)(de)(de)特征，存(cun)在(zai)(zai)(zai)(zai)(zai)潛在(zai)(zai)(zai)(zai)(zai)的(de)(de)(de)(de)(de)(de)(de)(de)(de)癌變(bian)(bian)風險(xian)。實際上，克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)個(ge)體(ti)(ti)罹患(huan)(huan)血(xue)(xue)液系統腫(zhong)瘤(liu)和(he)早(zao)逝(shi)的(de)(de)(de)(de)(de)(de)(de)(de)(de)風險(xian)更高(gao)(gao)。令人驚(jing)訝(ya)的(de)(de)(de)(de)(de)(de)(de)(de)(de)是，雖然(ran)部(bu)(bu)分(fen)(fen)(fen)(fen)增(zeng)(zeng)(zeng)(zeng)加的(de)(de)(de)(de)(de)(de)(de)(de)(de)死(si)亡(wang)率是由于(yu)血(xue)(xue)液系統腫(zhong)瘤(liu)，但大(da)部(bu)(bu)分(fen)(fen)(fen)(fen)可(ke)以(yi)(yi)歸結為(wei)(wei)(wei)吸(xi)(xi)煙(yan)(yan)相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)疾(ji)(ji)病。克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)不僅增(zeng)(zeng)(zeng)(zeng)加了(le)(le)(le)(le)(le)罹患(huan)(huan)血(xue)(xue)液系統腫(zhong)瘤(liu)的(de)(de)(de)(de)(de)(de)(de)(de)(de)風險(xian)，對(dui)患(huan)(huan)慢性(xing)(xing)(xing)(xing)(xing)阻塞性(xing)(xing)(xing)(xing)(xing)肺病、肺癌、外(wai)周動脈疾(ji)(ji)病、肺氣腫(zhong)和(he)酗酒風險(xian)的(de)(de)(de)(de)(de)(de)(de)(de)(de)增(zeng)(zeng)(zeng)(zeng)加也(ye)有(you)(you)(you)(you)(you)明(ming)(ming)顯的(de)(de)(de)(de)(de)(de)(de)(de)(de)聯系。然(ran)而，此(ci)(ci)項研(yan)(yan)究(jiu)并未發現(xian)證(zheng)據(ju)(ju)支持廣(guang)為(wei)(wei)(wei)流(liu)傳(chuan)的(de)(de)(de)(de)(de)(de)(de)(de)(de)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)與(yu)心血(xue)(xue)管疾(ji)(ji)病之間(jian)的(de)(de)(de)(de)(de)(de)(de)(de)(de)聯系。研(yan)(yan)究(jiu)發現(xian)，吸(xi)(xi)煙(yan)(yan)對(dui)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)有(you)(you)(you)(you)(you)劑(ji)量(liang)依賴(lai)性(xing)(xing)(xing)(xing)(xing)影響，并可(ke)能(neng)(neng)隨著(zhu)年齡的(de)(de)(de)(de)(de)(de)(de)(de)(de)增(zeng)(zeng)(zeng)(zeng)長而加速(su)其(qi)(qi)進展。這(zhe)表明(ming)(ming)，克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)在(zai)(zai)(zai)(zai)(zai)某(mou)些(xie)(xie)(xie)方(fang)面可(ke)作為(wei)(wei)(wei)吸(xi)(xi)煙(yan)(yan)的(de)(de)(de)(de)(de)(de)(de)(de)(de)標志(zhi)，而非(fei)血(xue)(xue)液病的(de)(de)(de)(de)(de)(de)(de)(de)(de)相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)性(xing)(xing)(xing)(xing)(xing)，其(qi)(qi)本質上是由吸(xi)(xi)煙(yan)(yan)行為(wei)(wei)(wei)和(he)高(gao)(gao)齡造(zao)(zao)(zao)(zao)成的(de)(de)(de)(de)(de)(de)(de)(de)(de)。接(jie)下來(lai)(lai)，在(zai)(zai)(zai)(zai)(zai)本研(yan)(yan)究(jiu)中(zhong)(zhong)，對(dui)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)遺(yi)傳(chuan)基礎進行了(le)(le)(le)(le)(le)調查(cha)。研(yan)(yan)究(jiu)首先(xian)關(guan)(guan)注 HSC 中(zhong)(zhong)可(ke)能(neng)(neng)出現(xian)的(de)(de)(de)(de)(de)(de)(de)(de)(de)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)，這(zhe)些(xie)(xie)(xie)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)使得某(mou)些(xie)(xie)(xie)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)細(xi)(xi)(xi)(xi)胞(bao)具有(you)(you)(you)(you)(you)選擇性(xing)(xing)(xing)(xing)(xing)優勢，從而能(neng)(neng)夠取代正常(chang)骨(gu)髓和(he)造(zao)(zao)(zao)(zao)血(xue)(xue)功能(neng)(neng)。研(yan)(yan)究(jiu)者(zhe)發現(xian)了(le)(le)(le)(le)(le)幾種所(suo)謂的(de)(de)(de)(de)(de)(de)(de)(de)(de)驅動突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)，其(qi)(qi)中(zhong)(zhong)許多(duo)(duo)與(yu)已知與(yu)骨(gu)髓和(he)淋(lin)巴腫(zhong)瘤(liu)有(you)(you)(you)(you)(you)關(guan)(guan)。然(ran)而，大(da)多(duo)(duo)數(shu)(shu) HSC 克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)都(dou)沒(mei)有(you)(you)(you)(you)(you)明(ming)(ming)顯的(de)(de)(de)(de)(de)(de)(de)(de)(de)驅動突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)，其(qi)(qi)為(wei)(wei)(wei)何會(hui)(hui)(hui)增(zeng)(zeng)(zeng)(zeng)殖仍然(ran)無(wu)從所(suo)知。針對(dui)易(yi)(yi)患(huan)(huan) CH 的(de)(de)(de)(de)(de)(de)(de)(de)(de)遺(yi)傳(chuan)變(bian)(bian)異(yi)(yi)，deCODE 發現(xian)了(le)(le)(le)(le)(le)25個(ge)與(yu)此(ci)(ci)相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)的(de)(de)(de)(de)(de)(de)(de)(de)(de)基因座發生了(le)(le)(le)(le)(le)變(bian)(bian)異(yi)(yi)。在(zai)(zai)(zai)(zai)(zai)某(mou)些(xie)(xie)(xie)情(qing)況(kuang)下，這(zhe)些(xie)(xie)(xie)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)顯示(shi)會(hui)(hui)(hui)影響與(yu) CH 相(xiang)(xiang)(xiang)(xiang)關(guan)(guan)的(de)(de)(de)(de)(de)(de)(de)(de)(de)基因表達、剪(jian)接(jie)或血(xue)(xue)漿蛋白(bai)水平。這(zhe)些(xie)(xie)(xie)突(tu)(tu)(tu)(tu)(tu)變(bian)(bian)通常(chang)也(ye)會(hui)(hui)(hui)影響血(xue)(xue)細(xi)(xi)(xi)(xi)胞(bao)數(shu)(shu)量(liang)、骨(gu)髓增(zeng)(zeng)(zeng)(zeng)生性(xing)(xing)(xing)(xing)(xing)腫(zhong)瘤(liu)和(he)白(bai)細(xi)(xi)(xi)(xi)胞(bao)端粒長度。總而言之，此(ci)(ci)項研(yan)(yan)究(jiu)為(wei)(wei)(wei)克(ke)(ke)(ke)隆(long)(long)(long)(long)(long)(long)(long)(long)性(xing)(xing)(xing)(xing)(xing)造(zao)(zao)(zao)(zao)血(xue)(xue)的(de)(de)(de)(de)(de)(de)(de)(de)(de)遺(yi)傳(chuan)學和(he)流(liu)行病學提供了(le)(le)(le)(le)(le)實質性(xing)(xing)(xing)(xing)(xing)的(de)(de)(de)(de)(de)(de)(de)(de)(de)洞(dong)見。

DeCODE 位于冰島雷克雅未克，是分析和解讀人類基因組的全球領軍企業。deCODE 已借助其獨特的專業知識和人口資源發現了數十種常見疾病的遺傳風險因素。了解疾病遺傳學的目的在于利用這些信息創造全新的疾病診療和預防方法。deCODE 是 Amgen（納斯達克股票代碼：AMGN）的全資子公司。